A three‐dimensional placoderm (stem‐group gnathostome) pharyngeal skeleton and its implications for primitive gnathostome pharyngeal architecture

The pharyngeal skeleton is a key vertebrate anatomical system in debates on the origin of jaws and gnathostome (jawed vertebrate) feeding. Furthermore, it offers considerable potential as a source of phylogenetic data. Well‐preserved examples of pharyngeal skeletons from stem‐group gnathostomes remain poorly known. Here, we describe an articulated, nearly complete pharyngeal skeleton in an Early Devonian placoderm fish, Paraplesiobatis heinrichsi Broili, from Hunsrück Slate of Germany. Using synchrotron light tomography, we resolve and reconstruct the three‐dimensional gill arch architecture of Paraplesiobatis and compare it with other gnathostomes. The preserved pharyngeal skeleton comprises elements of the hyoid arch (probable ceratohyal) and a series of branchial arches. Limited resolution in the tomography scan causes some uncertainty in interpreting the exact number of arches preserved. However, at least four branchial arches are present. The final and penultimate arches are connected as in osteichthyans. A single median basihyal is present as in chondrichthyans. No dorsal (epibranchial or pharyngobranchial) elements are observed. The structure of the pharyngeal skeleton of Paraplesiobatis agrees well with Pseudopetalichthys from the same deposit, allowing an alternative interpretation of the latter taxon. The phylogenetic significance of Paraplesiobatis is considered. A median basihyal is likely an ancestral gnathostome character, probably with some connection to both the hyoid and the first branchial arch pair. Unpaired basibranchial bones may be independently derived in chondrichthyans and osteichthyans.A three‐dimensional articulated gill arch skeleton of a 400‐million‐year‐old placoderm fish is described. This adds to the diversity of feeding and respiratory structures in jawed vertebrate animals and informing hypotheses of gill arch evolution in the first jawed vertebrates.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138208/1/jmor20706_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138208/2/jmor20706.pd

Endochondral bone in an Early Devonian ‘placoderm’ from Mongolia

Endochondral bone is the main internal skeletal tissue of nearly all osteichthyans—the group comprising more than 60,000 living species of bony fishes and tetrapods. Chondrichthyans (sharks and their kin) are the living sister group of osteichthyans and have primarily cartilaginous endoskeletons, long considered the ancestral condition for all jawed vertebrates (gnathostomes). The absence of bone in modern jawless fishes and the absence of endochondral ossification in early fossil gnathostomes appear to lend support to this conclusion. Here we report the discovery of extensive endochondral bone in Minjinia turgenensis, a new genus and species of ‘placoderm’-like fish from the Early Devonian (Pragian) of western Mongolia described using X-ray computed microtomography. The fossil consists of a partial skull roof and braincase with anatomical details providing strong evidence of placement in the gnathostome stem group. However, its endochondral space is filled with an extensive network of fine trabeculae resembling the endochondral bone of osteichthyans. Phylogenetic analyses place this new taxon as a proximate sister group of the gnathostome crown. These results provide direct support for theories of generalized bone loss in chondrichthyans. Furthermore, they revive theories of a phylogenetically deeper origin of endochondral bone and its absence in chondrichthyans as a secondary condition

A well-preserved ‘placoderm’ (stem-group Gnathostomata) upper jaw from the Early Devonian of Mongolia clarifies jaw evolution

The origin of jaws and teeth remains contentious in vertebrate evolution. ‘Placoderms’ (Silurian-Devonian armoured jawed fishes) are central to debates on the origins of these anatomical structures. ‘Acanthothoracids’ are generally considered the most primitive ‘placoderms’. However, they are so far known mainly from disarticulated skeletal elements that are typically incomplete. The structure of the jaws—particularly the jaw hinge—is poorly known, leaving open questions about their jaw function and comparison with other placoderms and modern gnathostomes. Here we describe a near-complete ‘acanthothoracid’ upper jaw, allowing us to reconstruct the likely orientation and angle of the bite and compare its morphology with that of other known ‘placoderm’ groups. We clarify that the bite position is located on the upper jaw cartilage rather than on the dermal cheek and thus show that there is a highly conserved bite morphology among most groups of ‘placoderms’, regardless of their overall cranial geometry. Incorporation of the dermal skeleton appears to provide a sound biomechanical basis for jaw origins. It appears that ‘acanthothoracid’ dentitions were fundamentally similar in location to that of arthrodire ‘placoderms’, rather than resembling bony fishes. Irrespective of current phylogenetic uncertainty, the new data here resolve the likely general condition for ‘placoderms’ as a whole, and as such, ancestral morphology of known jawed vertebrates

A revision of Vernicomacanthus Miles with comments on the characters of stem-group chondrichthyans

International audiencehe ‘acanthodian’ fishes provide key anatomical insights into the deepest branches of the chondrichthyan stem group. We review the anatomy of the acanthodian Vernicomacanthus uncinatus from the Lochkovian (Lower Devonian, 419.2–410.8 Ma) of Scotland based on eight articulated fossils, one of which is newly described. Broadly, the anatomy of V. uncinatus fits with that of contemporaneous acanthodians such as Climatius and Parexus, with a head covered by robust tesserae, an enlarged postorbital scale, an armoured shoulder girdle, and many pairs of ventrolateral spines. However, it departs from this anatomy in key respects. Its pectoral fin spines are obliquely ridged and posteriorly denticulated, similarly to Carboniferous gyracanth stem-group chondrichthyans. Its scales consist of multiple anteroposteriorly aligned odontodes, similarly to many Palaeozoic ‘sharks’. And its endoskeletal shoulder girdle may have a posterolateral angle, previously observed only in shark-like chondrichthyans. We propose that the differences between V. uncinatus and its congeneric, V. waynensis, which include potentially phylogenetically significant characters of the shoulder girdle and spines, are sufficient to erect a new genus for V. waynensis:Dobunnacanthus gen. nov. The scales of Vernicomacanthus are identical to those of the ‘shark’ scale genus Altholepis, suggesting that some such scales may instead belong to taxa with acanthodian-like gross anatomies. Based on these scales we highlight potential patterns in chondrichthyan scale evolution, in particular the axial addition of odontodes. Anatomical similarities between Vernicomacanthus and gyracanths, highlighted by previous authors, may indicate the existence of a grade including these and similar acanthodian-grade taxa placed relatively crownwards in the chondrichthyan stem-grou

The braincase and jaws of a Devonian 'acanthodian' and modern gnathostome origins.

Modern gnathostomes (jawed vertebrates) emerged in the early Palaeozoic era, but this event remains unclear owing to a scant early fossil record. The exclusively Palaeozoic acanthodians are possibly the earliest gnathostome group and exhibit a mosaic of shark- and bony fish-like characters that has long given them prominence in discussions of early gnathostome evolution. Their relationships with modern gnathostomes have remained mysterious, partly because their un-mineralized endoskeletons rarely fossilized. Here I present the first-known braincase of an Early Devonian (approximately 418-412 Myr bp) acanthodian, Ptomacanthus anglicus, and re-evaluate the interrelationships of basal gnathostomes. Acanthodian braincases have previously been represented by a single genus, Acanthodes, which occurs more than 100 million years later in the fossil record. The braincase of Ptomacanthus differs radically from the osteichthyan-like braincase of Acanthodes in exhibiting several plesiomorphic features shared with placoderms and some early chondrichthyans. Most striking is its extremely short sphenoid region and its jaw suspension, which displays features intermediate between some Palaeozoic chondrichthyans and osteichthyans. Phylogenetic analysis resolves Ptomacanthus as either the most basal chondrichthyan or as the sister group of all living gnathostomes. These new data alter earlier conceptions of basal gnathostome phylogeny and thus help to provide a more detailed picture of the acquisition of early gnathostome characters

Correlates of physical activity and sitting time in adults with type 2 diabetes attending primary health care in Oman

Abstract Background Despite evidence of the benefits of physical activity in the management of type 2 diabetes, it is poorly addressed in diabetes care. This study aimed to identify the prevalence and correlates of meeting ≥600MET-min/wk. (150 min/wk) of physical activity and sitting time in adults with type 2 diabetes in Oman. Approaches to encourage physical activity in diabetes care were explored. Methods A cross-sectional study using the Global Physical Activity Questionnaire was conducted in 17 randomly selected primary health centres in Muscat. Clinical data including co-morbidities were extracted from the health information system. Questions on physical activity preferences and approaches were included. Patients were approached if they were ≥18 years, and had been registered in the diabetes clinic for >2 years. Results The questionnaire was completed by 305 people (females 57% and males 43%). Mean age (SD) was 57 (10.8) years and mean BMI (SD) was 31.0 (6.0) kg/m2. Duration of diabetes ranged from 2 to 25 (mean 7.6) years. Hypertension (71%) and dyslipidaemia (62%) were common comorbidities. Most (58.4%) had an HbA1c ≥7% indicating poor glycaemic control (55% in males vs 61% in females). Physical activity recommendations were met by 21.6% of the participants, mainly through leisure activities. Odds of meeting the recommendations were significantly higher in males (OR 4.8, 95% CI 2.5–9.1), individuals ≤57 years (OR 3.0, 95% CI 1.6–5.9), those at active self-reported stages of change for physical activity (OR 2.2, 95% CI 1.2–4.1) and those reporting no barriers to performing physical activity (OR 2.7, 95% CI 1.4–4.9). Median (25th, 75th percentiles) sitting time was 705 (600, 780) min/d. Older age (>57 years) was associated with longer sitting time (>705 min/d) (OR 2.8, 95% CI 1.7–4.6). Preferred methods to support physical activity in routine diabetes care were consultations (38%), structured physical activity sessions (13.4%) and referrals to physical activity facilities (5.6%) delivered by a variety of health care providers. Conclusions The results suggest that intervention strategies should take account of gender, age, opportunities within daily life to promote active behaviour and readiness to change. Offering physical activity consultations is of interest to this study population, thus development and evaluation of interventions are warranted

Basal fatty acid oxidation increases after recurrent low glucose in human primary astrocytes

YesAims/hypothesis Hypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG). Methods To test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios. Results AMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure. Conclusions/interpretation Taken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes.Diabetes UK (RD Lawrence Fellowship to CB; 13/0004647); the Medical Research Council (MR/N012763/1) to KLJE, ADR and CB; and a Mary Kinross Charitable Trust PhD studentship to CB, ADR and RW to support PGWP. Additional support for this work came from awards from the British Society for Neuroendocrinology (to CB and KLJE), the Society for Endocrinology (CB), Tenovus Scotland (CB) and the University of Exeter Medical School (CB and KLJE). AR was also supported by a Royal Society Industry Fellowship

An ancient dental gene network regulates development and continuous regeneration of teeth in sharks

The appearance of toothed vertebrates has proven a major determinant of the overall success of this lineage. This is most apparent in sharks and rays (elasmobranchs), which further retain the capacity for life-long tooth regeneration. Given their comparatively basal phylogenetic position, elasmobranchs therefore offer the opportunity for crucial insights into putative ancestral characters of tooth development, yet despite their evolutionary significance this remains poorly understood. Using the established chondrichthyan model, the catshark (Scyliorhinus sp.), we identified the expression of genes representative of conserved signaling pathways during stages of early dental competence, tooth initiation and regeneration. The expression patterns of β-catenin, shh, bmp4, pax9, pitx1/2, and the stem cell marker Sox2, characterise an ancestrally conserved gene set deployed during initiation of the elasmobranch dentition, suggesting that all vertebrate dentitions are defined by the expression of this core set of genes. These findings provide novel evidence to support the conservation in deep evolutionary time of a core set of dental patterning genes, therefore further defining the evolutionary trajectory of tooth development. We show how these genes facilitate the emergence of the shark dentition and offer insights into their deployment during development of the dental lamina, a sheet of dental epithelial cells that are responsible for continuous tooth regeneration. This study further promotes a specific experimental agenda to further characterise the roles of these core developmental genes during vertebrate tooth development, and importantly dental regeneration

Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms

Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV) recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN) response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR)-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses