The internationalisation of the Spanish SME sector

As part of a wider research program, we analysed the theoretical framework and the recent developments of the process of internationalisation (transnationalisation) of the small- and medium-sized enterprises in Spain. The paper highlights the main trends and barriers of this internationalisation process. Methodology included document analyses, interviews, and the analyses of statistical databases

Cutting blade dentitions in squaliform sharks form by modification of inherited alternate tooth ordering patterns

The squaliform sharks represent one of the most speciose shark clades. Many adult squaliforms have blade-like teeth, either on both jaws or restricted to the lower jaw, forming a continuous, serrated blade along the jaw margin. These teeth are replaced as a single unit and successor teeth lack the alternate arrangement present in other elasmobranchs. Micro-CT scans of embryos of squaliforms and a related outgroup (Pristiophoridae) revealed that the squaliform dentition pattern represents a highly modified version of tooth replacement seen in other clades. Teeth of Squalus embryos are arranged in an alternate pattern, with successive tooth rows containing additional teeth added proximally. Asynchronous timing of tooth production along the jaw and tooth loss prior to birth cause teeth to align in oblique sets containing teeth from subsequent rows; these become parallel to the jaw margin during ontogeny, so that adult Squalus has functional tooth rows comprising obliquely stacked teeth of consecutive developmental rows. In more strongly heterodont squaliforms, initial embryonic lower teeth develop into the oblique functional sets seen in adult Squalus, with no requirement to form, and subsequently lose, teeth arranged in an initial alternate pattern

Ecological impact of the end-Cretaceous extinction on lamniform sharks

Lamniform sharks are apex marine predators undergoing dramatic local and regional decline worldwide, with consequences for marine ecosystems that are difficult to predict. Through their long history, lamniform sharks have faced widespread extinction, and understanding those ‘natural experiments’ may help constrain predictions, placing the current crisis in evolutionary context. Here we show, using novel morphometric analyses of fossil shark teeth, that the end-Cretaceous extinction of many sharks had major ecological consequences. Post-extinction ecosystems supported lower diversity and disparity of lamniforms, and were dominated by significantly smaller sharks with slimmer, smoother and less robust teeth. Tooth shape is intimately associated with ecology, feeding and prey type, and by integrating data from extant sharks we show that latest Cretaceous sharks occupied similar niches to modern lamniforms, implying similar ecosystem structure and function. By comparison, species in the depauperate post-extinction community occupied niches most similar to those of juvenile sand tigers (Carcharias taurus). Our data show that quantitative tooth morphometrics can distinguish lamniform sharks due to dietary differences, providing critical insights into ecological consequences of past extinction episodes

Early development of rostrum saw-teeth in a fossil ray tests classical theories of the evolution of vertebrate dentitions

In classical theory, teeth of vertebrate dentitions evolved from co-option of external skin denticles into the oral cavity. This hypothesis predicts that ordered tooth arrangement and regulated replacement in the oral dentition were also derived from skin denticles. The fossil batoid ray Schizorhiza stromeri (Chondrichthyes; Cretaceous) provides a test of this theory. Schizorhiza preserves an extended cartilaginous rostrum with closely spaced, alternating saw-teeth, different from sawfish and sawsharks today. Multiple replacement teeth reveal unique new data from micro-CT scanning, showing how the 'cone-in-cone' series of ordered saw-teeth sets arrange themselves developmentally, to become enclosed by the roots of pre-existing saw-teeth. At the rostrum tip, newly developing saw-teeth are present, as mineralized crown tips within a vascular, cartilaginous furrow; these reorient via two 90° rotations then relocate laterally between previously formed roots. Saw-tooth replacement slows mid-rostrum where fewer saw-teeth are regenerated. These exceptional developmental data reveal regulated order for serial self-renewal, maintaining the saw edge with ever-increasing saw-tooth size. This mimics tooth replacement in chondrichthyans, but differs in the crown reorientation and their enclosure directly between roots of predecessor saw-teeth. Schizorhiza saw-tooth development is decoupled from the jaw teeth and their replacement, dependent on a dental lamina. This highly specialized rostral saw, derived from diversification of skin denticles, is distinct from the dentition and demonstrates the potential developmental plasticity of skin denticles

Fossil evidence for a pharyngeal origin of the vertebrate pectoral girdle

The origin of vertebrate paired appendages is one of the most investigated and debated examples of evolutionary novelty. Paired appendages are widely considered key innovations that allowed new opportunities for controlled swimming and gill ventilation and were prerequisites for the eventual transition from water to land. The last 150 years of debate has been shaped by two contentious theories: the ventrolateral fin-fold hypothesis and the archipterygium hypothesis. The latter proposes that fins and girdles evolved from an ancestral gill arch. Although tantalizing developmental evidence has revived interest in this idea, it is apparently unsupported by fossil evidence. Here we present fossil evidence of a pharyngeal basis for the vertebrate shoulder girdle. We use CT scanning to reveal details of the braincase of Kolymaspis sibirica, a placoderm fish from the Early Devonian of Siberia that suggests a pharyngeal component of the shoulder. We combine these findings with refreshed comparative anatomy of placoderms and jawless outgroups to place the origin of the shoulder girdle on the sixth branchial arch. These findings provide a novel framework for understanding the origin of the pectoral girdle. Our new evidence clarifies the location of the presumptive head-trunk interface in jawless fishes and explains the constraint on branchial arch number in gnathostomes. The results revive a key aspect of the archipterygium hypothesis, but also reconciles it with the ventrolateral fin fold model

Mineralization of the Callorhinchus Vertebral Column (Holocephali; Chondrichthyes)

Members of the Chondrichthyes (Elasmobranchii and Holocephali) are distinguished by their largely cartilaginous endoskeletons, which comprise an uncalcified core overlain by a mineralized layer; in the Elasmobranchii (sharks, skates, rays) most of this mineralization takes the form of calcified polygonal tiles known as tesserae. In recent years, these skeletal tissues have been described in ever increasing detail in sharks and rays, but those of Holocephali (chimaeroids) have been less well-studied, with conflicting accounts as to whether or not tesserae are present. During embryonic ontogeny in holocephalans, cervical vertebrae fuse to form a structure called the synarcual. The synarcual mineralizes early and progressively, anteroposteriorly and dorsoventrally, and therefore presents a good skeletal structure in which to observe mineralized tissues in this group. Here, we describe the development and mineralization of the synarcual in an adult and stage 36 elephant shark embryo (Callorhinchus milii). Small, discrete, but irregular blocks of cortical mineralization are present in stage 36, similar to what has been described recently in embryos of other chimaeroid taxa such as Hydrolagus, while in Callorhinchus adults, the blocks of mineralization are more irregular, but remain small. This differs from fossil members of the holocephalan crown group (Edaphodon), as well as from stem group holocephalans (e.g., Symmorida, Helodus, Iniopterygiformes), where tesserae are notably larger than in Callorhinchus and show similarities to elasmobranch tesserae, for example with respect to polygonal shape

Development and evolution of tooth renewal in neoselachian sharks as a model for transformation in chondrichthyan dentitions

A defining feature of dentitions in modern sharks and rays is the regulated pattern order that generates multiple replacement teeth. These are arranged in labio‐lingual files of replacement teeth that form in sequential time order both along the jaw and within successively initiated teeth in a deep dental lamina. Two distinct adult dentitions have been described: alternate, in which timing of new teeth alternates between two adjacent files, each erupting separately, and the other arranged as single files, where teeth of each file are timed to erupt together, in some taxa facilitating similarly timed teeth to join to form a cutting blade. Both are dependent on spatiotemporally regulated formation of new teeth. The adult Angel shark Squatina (Squalomorphii) exemplifies a single file dentition, but we obtained new data on the developmental order of teeth in the files of Squatina embryos, showing alternate timing of tooth initiation. This was based on micro‐CT scans revealing that the earliest mineralised teeth at the jaw margin and their replacements in file pairs (odd and even jaw positions) alternate in their initiation timing. Along with Squatina, new observations from other squalomorphs such as Hexanchus and Chlamydoselachus, together with representatives of the sister group Galeomorphii, have established that the alternate tooth pattern (initiation time and replacement order) characterises the embryonic dentition of extant sharks; however, this can change in adults. These character states were plotted onto a recent phylogeny, demonstrating that the Squalomorphii show considerable plasticity of dental development. We propose a developmental‐evolutionary model to allow change from the alternate to a single file alignment of replacement teeth. This establishes new dental morphologies in adult sharks from inherited alternate order

Study of the p p -> p p pi+ pi- Reaction in the Low-Energy Tail of the Roper Resonance

Exclusive measurements of the p p -> p p pi+ pi- reaction have been carried out at Tp = 775 MeV at CELSIUS using the PROMICE/WASA setup. Together with data obtained at lower energy they point to a dominance of the Roper excitation in this process. From the observed interference of its decay routes N* -> N sigma and N* -> Delta pi -> N sigma their energy-dependent relative branching ratio is determined

Bricks, trusses and superstructures: strategies for skeletal reinforcement in batted fishes (rays and skates)

Crushing and eating hard prey (durophagy) is mechanically demanding. The cartilage jaws of durophagous stingrays are known to be reinforced relative to non-durophagous relatives, with a thickened external cortex of mineralized blocks (tesserae), reinforcing struts inside the jaw (trabeculae), and pavement-like dentition. These strategies for skeletal strengthening against durophagy, however, are largely understood only from myliobatiform stingrays, although a hard prey diet has evolved multiple times in batoid fishes (rays, skates, guitarfishes). We perform a quantitative analysis of micro-CT data, describing jaw strengthening mechanisms in Rhina ancylostoma (Bowmouth Guitarfish) and Rhynchobatus australiae (White-spotted Wedgefish), durophagous members of the Rhinopristiformes, the sister taxon to Myliobatiformes. Both species possess trabeculae, more numerous and densely packed in Rhina, albeit simpler structurally than those in stingrays like Aetobatus and Rhinoptera. Rhina and Rhynchobatus exhibit impressively thickened jaw cortices, often involving >10 tesseral layers, most pronounced in regions where dentition is thickest, particularly in Rhynchobatus. Age series of both species illustrate that tesserae increase in size during growth, with enlarged and irregular tesserae associated with the jaws’ oral surface in larger (older) individuals of both species, perhaps a feature of ageing. Unlike the flattened teeth of durophagous myliobatiform stingrays, both rhinopristiform species have oddly undulating dentitions, comprised of pebble-like teeth interlocked to form compound “meta-teeth” (large spheroidal structures involving multiple teeth). This is particularly striking in Rhina, where the upper/lower occlusal surfaces are mirrored undulations, fitting together like rounded woodworking finger-joints. Trabeculae were previously thought to have arisen twice independently in Batoidea; our results show they are more widespread among batoid groups than previously appreciated, albeit apparently absent in the phylogenetically basal Rajiformes. Comparisons with several other durophagous and non-durophagous species illustrate that batoid skeletal reinforcement architectures are modular: trabeculae can be variously oriented and are dominant in some species (e.g. Rhina, Aetobatus), whereas cortical thickening is more significant in others (e.g. Rhynchobatus), or both reinforcing features can be lacking (e.g. Raja, Urobatis). We discuss interactions and implications of character states, framing a classification scheme for exploring cartilage structure evolution in the cartilaginous fishes

Gut microbiota‐dependent trimethylamine N‐oxide and cardiovascular outcomes in patients with prior myocardial infarction: A nested case control study from the PEGASUS‐TIMI 54 trial

Background Trimethylamine N‐oxide (TMAO) may have prothrombotic properties. We examined the association of TMAO quartiles with major adverse cardiovascular events (MACE) and the effect of TMAO on the efficacy of ticagrelor. Methods and Results PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin ‐ Thrombolysis in Myocardial Infarction 54) randomized patients with prior myocardial infarction to ticagrelor or placebo (median follow‐up 33 months). Baseline plasma concentrations of TMAO were measured in a nested case‐control study of 597 cases with cardiovascular death, myocardial infarction, or stroke (MACE) and 1206 controls matched for age, sex, and estimated glomerular filtration rate [eGFR]. Odds ratios (OR) were used for the association between TMAO quartiles and MACE, adjusting for baseline clinical characteristics (age, sex, eGFR, region, body mass index, hypertension, hypercholesterolemia, diabetes mellitus, smoking, peripheral artery disease, index event, aspirin dosage and treatment arm), and cardiovascular biomarkers (hs‐TnT [high‐sensitivity troponin T], hs‐CRP [high‐sensitivity C‐reactive protein], NT‐proBNP [N‐terminal‐pro‐B‐type natriuretic peptide]). Higher TMAO quartiles were associated with risk of MACE (OR for quartile 4 versus quartile 1, 1.43, 95% CI, 1.06–1.93, P trend=0.015). The association was driven by cardiovascular death (OR 2.25, 95% CI, 1.28–3.96, P trend=0.003) and stroke (OR 2.68, 95% CI, 1.39–5.17, P trend<0.001). After adjustment for clinical factors, the association persisted for cardiovascular death (ORadj 1.89, 95% CI, 1.03–3.45, P trend=0.027) and stroke (ORadj 2.01, 95% CI, 1.01–4.01, P trend=0.022), but was slightly attenuated after adjustment for cardiovascular biomarkers (cardiovascular death: ORadj 1.74, 95% CI, 0.88–3.45, P trend=0.079; and stroke: ORadj 1.82, 95% CI, 0.88–3.78, P trend=0.056). The reduction in MACE with ticagrelor was consistent across TMAO quartiles (P interaction=0.92). Conclusions Among patients with prior myocardial infarction, higher TMAO levels were associated with cardiovascular death and stroke but not with recurrent myocardial infarction. The efficacy of ticagrelor was consistent regardless of TMAO levels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifiers: PEGASUS‐TIMI 54, NCT01225562