Distortion of Globular Clusters by Galactic Bulges

One of the external fields that influences the population of globular clusters is that due to galactic bulges. In extreme situations, perigalactic distances $r_p \le 100$ pc, globular clusters could suffer total disruption in a single passage. A more common scenario is that for cluster orbits with $r_p \ge 200$ pc. We investigate the effects of tidal forces from a bulge on the shape of globular clusters for this type of encounters. We find distortions characterized by ``twisting isophotes'' and consider the potential for observability of this effect. In the Milky Way, a typical globular cluster must pass within several hundred pc of the center to experience substantial distortion, and it is possible that this has happened recently to one or two present day clusters. We estimate that this distortion could be observed even for globulars in dense fields toward the bulge. In more extreme environments such as giant ellipticals or merger products with newly formed globulars, this effect could be more common, extending out to orbits that pass within 1 kpc of the bulge center. This would lead to a substantial shift in the eccentricity distribution of globulars in those galaxies.Comment: 12 pages, 8 figure

Plastid Transcript Editing across Dinoflagellate Lineages Shows Lineage-Specific Application but Conserved Trends.

Dinoflagellates are a group of unicellular protists with immense ecological and evolutionary significance and cell biological diversity. Of the photosynthetic dinoflagellates, the majority possess a plastid containing the pigment peridinin, whereas some lineages have replaced this plastid by serial endosymbiosis with plastids of distinct evolutionary affiliations, including a fucoxanthin pigment-containing plastid of haptophyte origin. Previous studies have described the presence of widespread substitutional RNA editing in peridinin and fucoxanthin plastid genes. Because reports of this process have been limited to manual assessment of individual lineages, global trends concerning this RNA editing and its effect on the biological function of the plastid are largely unknown. Using novel bioinformatic methods, we examine the dynamics and evolution of RNA editing over a large multispecies data set of dinoflagellates, including novel sequence data from the peridinin dinoflagellate Pyrocystis lunula and the fucoxanthin dinoflagellate Karenia mikimotoi. We demonstrate that while most individual RNA editing events in dinoflagellate plastids are restricted to single species, global patterns, and functional consequences of editing are broadly conserved. We find that editing is biased toward specific codon positions and regions of genes, and generally corrects otherwise deleterious changes in the genome prior to translation, though this effect is more prevalent in peridinin than fucoxanthin lineages. Our results support a model for promiscuous editing application subsequently shaped by purifying selection, and suggest the presence of an underlying editing mechanism transferred from the peridinin-containing ancestor into fucoxanthin plastids postendosymbiosis, with remarkably conserved functional consequences in the new lineage

Progressive and biased divergent evolution underpins the origin and diversification of peridinin dinoflagellate plastids

Dinoflagellates are algae of tremendous importance to ecosystems and to public health. The cell biology and genome organization of dinoflagellate species is highly unusual. For example, the plastid genomes of peridinin-containing dinoflagellates encode only a minimal number of genes arranged on small elements termed "minicircles". Previous studies of peridinin plastid genes have found evidence for divergent sequence evolution, including extensive substitutions, novel insertions and deletions, and use of alternative translation initiation codons. Understanding the extent of this divergent evolution has been hampered by the lack of characterized peridinin plastid sequences. We have identified over 300 previously unannotated peridinin plastid mRNAs from published transcriptome projects, vastly increasing the number of sequences available. Using these data, we have produced a well-resolved phylogeny of peridinin plastid lineages, which uncovers several novel relationships within the dinoflagellates. This enables us to define changes to plastid sequences that occurred early in dinoflagellate evolution, and that have contributed to the subsequent diversification of individual dinoflagellate clades. We find that the origin of the peridinin dinoflagellates was specifically accompanied by elevations both in the overall number of substitutions that occurred on plastid sequences, and in the Ka/Ks ratio associated with plastid sequences, consistent with changes in selective pressure. These substitutions, alongside other changes, have accumulated progressively in individual peridinin plastid lineages. Throughout our entire dataset, we identify a persistent bias toward non-synonymous substitutions occurring on sequences encoding photosystem I subunits and stromal regions of peridinin plastid proteins, which may have underpinned the evolution of this unusual organelle.Wellcome Trus

Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Group recommended a panel of mutations and variants that should be tested to determine carrier status within the CFTR gene as a part of population screening programs.1,2 This was initially done in response to the recommendations of an NIH CF Consensus Conference that CF carrier screening be consid-ered by all couples for use before conception or prenatally.3 At that time, the Working Group recognized limitations in our understanding of the population frequencies of several CF al-leles and proposed to review mutation distribution data after the first two years of the program. In 2002, as part of an ongo-ing effort to ensure that the cystic fibrosis carrier screening programs are current with respect to the scientific literature and other available data and practices, we initiated a second review of data on the distribution of mutations in different ethnic groups and we began to assess whether providers wer

Different Effect of Proteasome Inhibition on Vesicular Stomatitis Virus and Poliovirus Replication

Proteasome activity is an important part of viral replication. In this study, we examined the effect of proteasome inhibitors on the replication of vesicular stomatitis virus (VSV) and poliovirus. We found that the proteasome inhibitors significantly suppressed VSV protein synthesis, virus accumulation, and protected infected cells from toxic effect of VSV replication. In contrast, poliovirus replication was delayed, but not diminished in the presence of the proteasome inhibitors MG132 and Bortezomib. We also found that inhibition of proteasomes stimulated stress-related processes, such as accumulation of chaperone hsp70, phosphorylation of eIF2α, and overall inhibition of translation. VSV replication was sensitive to this stress with significant decline in replication process. Poliovirus growth was less sensitive with only delay in replication. Inhibition of proteasome activity suppressed cellular and VSV protein synthesis, but did not reduce poliovirus protein synthesis. Protein kinase GCN2 supported the ability of proteasome inhibitors to attenuate general translation and to suppress VSV replication. We propose that different mechanisms of translational initiation by VSV and poliovirus determine their sensitivity to stress induced by the inhibition of proteasomes. To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection

The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC

Evolution and extinction of Maastrichtian (Late Cretaceous) cephalopods from the López de Bertodano Formation, Seymour Island, Antarctica

One of the most expanded records to contain the final fortunes of ammonoid cephalopods is within the López de Bertodano Formation of Seymour Island, James Ross Basin, Antarctica. Located at 65° South now, and during the Cretaceous, this sequence is the highest southern latitude onshore outcrop containing the Cretaceous-Paleogene (K-Pg) transition. We present comprehensive new biostratigraphic range data for 14 ammonite and one nautiloid species based on the collection of >. 700 macrofossils from high-resolution sampling of parallel sedimentary sections, dated Maastrichtian to earliest Danian in age, across southern Seymour Island. We find evidence for only a single, abrupt pulse of cephalopod extinction at the end of the Cretaceous when the final seven ammonite species disappeared, consistent with most evidence globally. In the lead up to the K-Pg extinction in the James Ross Basin, starting during the Campanian, ammonite diversity decreased overall, but the number of endemic taxa belonging to the family Kossmaticeratidae actually increased. This pattern continued into the Maastrichtian and may be facies controlled, linked to changes in sea level and seawater temperature. During the early Maastrichtian, ammonite diversity dropped significantly with only two species recorded from the basal López de Bertodano Formation on Seymour Island. The subsequent diversification of endemic taxa and reappearance of long-ranging, widespread species into the basin resulted in an increase in ammonite diversity and abundance during the mid-Maastrichtian. This was coincident with an apparent period of warming temperatures and sea level rise interpreted from palynology and sedimentology, perhaps reflecting a high latitude expression of the Mid-Maastrichtian Event. Late Maastrichtian diversity levels remained stable despite reported climatic and environmental variation. Ammonite diversity patterns during the Maastrichtian parallel those of microfossil species such as nannofossil and planktonic foraminifera, suggesting that dynamic climatic and environmental changes affected many planktonic and nektonic organisms during the latest Cretaceous. However, we suggest that these perturbations had a minimal effect on overall diversity prior to the catastrophic extinction event at the K-Pg boundary

Prediction Scores Do Not Correlate with Clinically Adjudicated Categories of Pulmonary Embolism in Critically Ill Patients

Copyright © 2014 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU).OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients.METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories.RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa 0.01 [95% CI −0.0643 to 0.0941]) or Wells pretest probabilities (kappa −0.03 [95% CI −0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30).CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Abstract: Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions: Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants