Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Multiple Orbitoides d’Orbigny lineages in the Maastrichtian? Data from the Central Sakarya Basin (Turkey) and Arabian Platform successions (Southeastern Turkey and Oman)

The standard reconstruction of species of Orbitoides d’Orbigny into a single lineage during the late Santonian to the end of the Maastrichtian is based upon morphometric data from Western Europe. An irreversible increase in the size of the embryonic apparatus, and the formation of a greater number of epi-embryonic chamberlets (EPC) with time, is regarded as the main evolutionary trends used in species discrimination. However, data from Maastrichtian Orbitoides assemblages from Central Turkey and the Arabian Platform margin (Southeastern Turkey and Oman) are not consistent with this record. The Maastrichtian Besni Formation of the Arabian Platform margin in Southeastern Turkey yields invariably biconvex specimens, with small, tri- to quadrilocular embryons and a small number of EPC, comparable to late Campanian Orbitoides medius (d’Archiac). The upper Maastrichtian Taraklı Formation from the Sakarya Basin of Central Turkey contains two distinct, yet closely associated forms of Orbitoides, easily differentiated by both external and internal features. Flat to biconcave specimens possess a small, tri- to quadrilocular embryonic apparatus of Orbitoides medius-type and a small number of EPC, whereas biconvex specimens possess a large, predominantly bilocular embryonic apparatus, and were assigned to Orbitoides ex. interc. gruenbachensis Papp–apiculatus Schlumberger based on morphometry. The flat to biconcave specimens belong to a long overlooked species Orbitoides pamiri Meriç, originally described from the late Maastrichtian of the Tauride Mountains in SW Turkey. This species is herein interpreted to be an offshoot from the main Orbitoides lineage during the Maastrichtian, as are forms that we term Orbitoides ‘medius’, since they recall this species, yet are younger than normal occurrence with the accepted morphometrically defined lineage. The consistent correlation between the external and internal test features in O. pamiri implies that the shape of the test is not an ecophenotypic variation, but appears to be biologically controlled. We, therefore, postulate that more than one lineage of Orbitoides exists during the Maastrichtian, with a lineage that includes O. ‘medius’ and O. pamiri displaying retrograde evolutionary features

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

Peer reviewe

Study of the production of charged pions, kaons, and protons in pPb collisions at √SNN=5.02 TeV

Peer reviewe

Measurements of the tt¯ charge asymmetry using the dilepton decay channel in pp collisions at √s=7 TeV

Peer reviewe

Transcriptional Repressor Gfi1 Integrates Cytokine-Receptor Signals Controlling B-Cell Differentiation

Hematopoietic stem cell differentiation is specified by cytokines and transcription factors, but the mechanisms controlling instructive and permissive signalling networks are poorly understood. We provide evidence that CLP1-dependent IL7-receptor mediated B cell differentiation is critically controlled by the transcriptional repressor Gfi1. Gfi1-deficient progenitor B cells show global defects in IL7Rα-dependent signal cascades. Consequently, IL7-dependent trophic, proliferative and differentiation-inducing responses of progenitor B cells are perturbed. Gfi1 directly regulates expression levels of IL7Rα and indirectly controls STAT5 signalling via expression of SOCS3. Thus, Gfi1 selectively specifies IL7-dependent development of B cells from CLP1 progenitors, providing clues to the transcriptional networks integrating cytokine signals and lymphoid differentiation

Vascular tube formation on matrix metalloproteinase-1-damaged collagen

Connective tissue damage and angiogenesis are both important features of tumour growth and invasion. Here, we show that endothelial cells maintained on a three-dimensional lattice of intact polymerised collagen formed a monolayer of cells with a cobblestone morphology. When the collagen was exposed to organ culture fluid from human basal cell tumours of the skin (containing a high level of active matrix metalloproteinase-1 (MMP-1)), degradation of the collagen matrix occurred. The major degradation products were the $3over 4$- and $1over 4$-sized fragments known to result from the action of MMP-1 on type I collagen. When endothelial cells were maintained on the partially degraded collagen, the cells organised into a network of vascular tubes. Pretreatment of the organ culture fluid with either tissue inhibitor of metalloproteinase-1 (TIMP-1) or neutralising antibody to MMP-1 prevented degradation of the collagen lattice and concomitantly inhibited endothelial cell organisation into the vascular network. Purified (activated) MMP-1 duplicated the effects of skin organ culture fluid, but other enzymes including MMP-9 (gelatinase B), elastase or trypsin failed to produce measurable fragments from intact collagen and also failed to promote vascular tube formation. Together, these studies suggest that damage to the collagenous matrix is itself an important inducer of new vessel formation