A Case of Spontaneous Intestinal Perforation in Osteogenesis Imperfecta

A 51-year-old male with known osteogenesis imperfecta (OI) (type 1) presented with symptoms and signs of infective endocarditis. Transthoracic echocardiography showed chordal rupture and free mitral regurgitation, resulting in an emergency mitral valve repair. The surgical procedure was largely uneventful but subsequent clinical course on the intensive care unit was complicated by bowel perforation requiring two laparatomies for a colonic resection and loop ileostomy formation. Histology of the excised tissue demonstrated absent musculature with no evidence of ischemia. Spontaneous non-ischemic bowel perforation as a complication of osteogenesis imperfecta is to date unreported. Our case highlights the need for a high index of suspicion of non-ischemic bowel perforation in patients with connective tissue disorders

Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. (c) 2008 Movement Disorder Society

Weak and Strong Lensing Statistics

After a brief introduction to gravitational lensing theory, a rough overview of the types of gravitational lensing statistics that have been performed so far will be given. I shall then concentrate on recent results of galaxy-galaxy lensing, which indicate that galactic halos extend much further than can be probed via rotation of stars and gas.Comment: 10 pages, 2 figures, talk given at the ISSI-Workshop "Matter in the Universe", 19-23 March 2001 Bern (Switzerland

A Substantial Population of Low Mass Stars in Luminous Elliptical Galaxies

The stellar initial mass function (IMF) describes the mass distribution of stars at the time of their formation and is of fundamental importance for many areas of astrophysics. The IMF is reasonably well constrained in the disk of the Milky Way but we have very little direct information on the form of the IMF in other galaxies and at earlier cosmic epochs. Here we investigate the stellar mass function in elliptical galaxies by measuring the strength of the Na I doublet and the Wing-Ford molecular FeH band in their spectra. These lines are strong in stars with masses <0.3 Msun and weak or absent in all other types of stars. We unambiguously detect both signatures, consistent with previous studies that were based on data of lower signal-to-noise ratio. The direct detection of the light of low mass stars implies that they are very abundant in elliptical galaxies, making up >80% of the total number of stars and contributing >60% of the total stellar mass. We infer that the IMF in massive star-forming galaxies in the early Universe produced many more low mass stars than the IMF in the Milky Way disk, and was probably slightly steeper than the Salpeter form in the mass range 0.1 - 1 Msun.Comment: To appear in Natur

PubChem3D: Diversity of shape

<p>Abstract</p> <p>Background</p> <p>The shape diversity of 16.4 million biologically relevant molecules from the PubChem Compound database and their 1.46 billion diverse conformers was explored as a function of molecular volume.</p> <p>Results</p> <p>The diversity of shape space was investigated by determining the shape similarity threshold to achieve a maximum on the count of reference shapes per unit of conformer volume. The rate of growth in shape space, as represented by a decreasing shape similarity threshold, was found to be remarkably smooth as a function of volume. There was no apparent correlation between the count of conformers per unit volume and their diversity, meaning that a single reference shape can describe the shape space of many chemical structures. The ability of a volume to describe the shape space of lesser volumes was also examined. It was shown that a given volume was able to describe 40-70% of the shape diversity of lesser volumes, for the majority of the volume range considered in this study.</p> <p>Conclusion</p> <p>The relative growth of shape diversity as a function of volume and shape similarity is surprisingly uniform. Given the distribution of chemicals in PubChem versus what is theoretically synthetically possible, the results from this analysis should be considered a conservative estimate to the true diversity of shape space.</p

Conserved motifs reveal details of ancestry and structure in the small tim chaperones of the mitochondrial intermembrane space

The mitochondrial inner and outer membranes are composed of a variety of integral membrane proteins, assembled into the membranes posttranslationally. The small translocase of the inner mitochondrial membranes (TIMs) are a group of ∼10 kDa proteins that function as chaperones to ferry the imported proteins across the mitochondrial intermembrane space to the outer and inner membranes. In yeast, there are 5 small TIM proteins: Tim8, Tim9, Tim10, Tim12, and Tim13, with equivalent proteins reported in humans. Using hidden Markov models, we find that many eukaryotes have proteins equivalent to the Tim8 and Tim13 and the Tim9 and Tim10 subunits. Some eukaryotes provide "snapshots" of evolution, with a single protein showing the features of both Tim8 and Tim13, suggesting that a single progenitor gene has given rise to each of the small TIMs through duplication and modification. We show that no "Tim12" family of proteins exist, but rather that variant forms of the cognate small TIMs have been recently duplicated and modified to provide new functions: the yeast Tim12 is a modified form of Tim10, whereas in humans and some protists variant forms of Tim9, Tim8, and Tim13 are found instead. Sequence motif analysis reveals acidic residues conserved in the Tim10 substrate-binding tentacles, whereas more hydrophobic residues are found in the equivalent substrate-binding region of Tim13. The substrate-binding region of Tim10 and Tim13 represent structurally independent domains: when the acidic domain from Tim10 is attached to Tim13, the Tim8–Tim13¹⁰ complex becomes essential and the Tim9–Tim10 complex becomes dispensable. The conserved features in the Tim10 and Tim13 subunits provide distinct binding surfaces to accommodate the broad range of substrate proteins delivered to the mitochondrial inner and outer membranes

The origin of dust in galaxies revisited: the mechanism determining dust content

The origin of cosmic dust is a fundamental issue in planetary science. This paper revisits the origin of dust in galaxies, in particular, in the Milky Way, by using a chemical evolution model of a galaxy composed of stars, interstellar medium, metals (elements heavier than helium), and dust. We start from a review of time-evolutionary equations of the four components, and then, we present simple recipes for the stellar remnant mass and yields of metal and dust based on models of stellar nucleosynthesis and dust formation. After calibrating some model parameters with the data from the solar neighborhood, we have confirmed a shortage of the stellar dust production rate relative to the dust destruction rate by supernovae if the destruction efficiency suggested by theoretical works is correct. If the dust mass growth by material accretion in molecular clouds is active, the observed dust amount in the solar neighborhood is reproduced. We present a clear analytic explanation of the mechanism for determining dust content in galaxies after the activation of accretion growth: a balance between accretion growth and supernova destruction. Thus, the dust content is independent of the uncertainty of the stellar dust yield after the growth activation. The timing of the activation is determined by a critical metal mass fraction which depends on the growth and destruction efficiencies. The solar system formation seems to have occurred well after the activation and plenty of dust would have existed in the proto-solar nebula.Comment: 12 pages, 11 figure

Mobile health in adults with congenital heart disease: Current use and future needs

Objective Many adults with congenital heart disease (CHD) are affected lifelong by cardiac events, particularly arrhythmias and heart failure. Despite the care provided, the cardiac event rate remains high. Mobile health (mHealth) brings opportunities to enhance daily monitoring and hence timely response in an attempt to improve outcome. However, it is not known if adults with CHD are currently using mHealth and what type of mHealth they may need in the near future. Methods Consecutive adult patients with CHD who visited the outpatient clinic at the Academic Medical Center in Amsterdam were asked to fill out questionnaires. Exclusion criteria for this study were mental impairment or inability to read and write Dutch. Results All 118 patients participated (median age 40 (range 18–78) years, 40 % male, 49 % symptomatic) and 92 % owned a smartphone. Whereas only a small minority (14 %) of patients used mHealth, the large majority (75 %) were willing to start. Most patients wanted to use mHealth in order to receive more information on physical health, and advice on progression of symptoms or signs of deterioration. Analyses on age, gender and complexity of defect showed significantly less current smartphone usage at older age, but no difference in interest or preferences in type of mHealth application for the near future. Conclusion The relatively young adult CHD population only rarely uses mHealth, but the majority are motivated to start using mHealth. New mHealth initiatives are required in these patients with a chronic condition who need lifelong surveillance in order to reveal if a reduction in morbidity and mortality and improvement in quality of life can be achieved

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom