Solitary median maxillary central incisor (SMMCI) syndrome

Solitary median maxillary central incisor syndrome (SMMCI) is a complex disorder consisting of multiple, mainly midline defects of development resulting from unknown factor(s) operating in utero about the 35th–38th day(s) from conception. It is estimated to occur in 1:50,000 live births. Aetiology is uncertain. Missense mutation in the SHH gene (I111F) at 7q36 may be associated with SMMCI. The SMMCI tooth differs from the normal central incisor, in that the crown form is symmetric; it develops and erupts precisely in the midline of the maxillary dental arch in both primary and permanent dentitions. Congenital nasal malformation (choanal atresia, midnasal stenosis or congenital pyriform aperture stenosis) is positively associated with SMMCI. The presence of an SMMCI tooth can predict associated anomalies and in particular the serious anomaly holoprosencephaly. Common congenital anomalies associated with SMMCI are: severe to mild intellectual disability, congenital heart disease, cleft lip and/or palate and less frequently, microcephaly, hypopituitarism, hypotelorism, convergent strabismus, oesophageal and duodenal atresia, cervical hemivertebrae, cervical dermoid, hypothyroidism, scoliosis, absent kidney, micropenis and ambiguous genitalia. Short stature is present in half the children. Diagnosis should be made by eight months of age, but can be made at birth and even prenatally at 18–22 weeks from the routine mid-trimester ultrasound scan. Management depends upon the individual anomalies present. Choanal stenosis requires emergency surgical treatment. Short stature may require growth hormone therapy. SMMCI tooth itself is mainly an aesthetic problem, which is ideally managed by combined orthodontic, prosthodontic and oral surgical treatment; alternatively, it can be left untreated

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Deletion of Exon 20 of the Familial Dysautonomia Gene Ikbkap in Mice Causes Developmental Delay, Cardiovascular Defects, and Early Embryonic Lethality

Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP - the protein encoded by Ikbkap - remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function

Low oxygen affects photophysiology and the level of expression of two-carbon metabolism genes in the seagrass <i>Zostera muelleri</i>

© 2017, Springer Science+Business Media B.V. Seagrasses are a diverse group of angiosperms that evolved to live in shallow coastal waters, an environment regularly subjected to changes in oxygen, carbon dioxide and irradiance. Zostera muelleri is the dominant species in south-eastern Australia, and is critical for healthy coastal ecosystems. Despite its ecological importance, little is known about the pathways of carbon fixation in Z. muelleri and their regulation in response to environmental changes. In this study, the response of Z. muelleri exposed to control and very low oxygen conditions was investigated by using (i) oxygen microsensors combined with a custom-made flow chamber to measure changes in photosynthesis and respiration, and (ii) reverse transcription quantitative real-time PCR to measure changes in expression levels of key genes involved in C4 metabolism. We found that very low levels of oxygen (i) altered the photophysiology of Z. muelleri, a characteristic of C3 mechanism of carbon assimilation, and (ii) decreased the expression levels of phosphoenolpyruvate carboxylase and carbonic anhydrase. These molecular-physiological results suggest that regulation of the photophysiology of Z. muelleri might involve a close integration between the C3 and C4, or other CO2 concentrating mechanisms metabolic pathways. Overall, this study highlights that the photophysiological response of Z. muelleri to changing oxygen in water is capable of rapid acclimation and the dynamic modulation of pathways should be considered when assessing seagrass primary production

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations.

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r rodents. Csf1r mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals