NanoStriDE: normalization and differential expression analysis of NanoString nCounter data

Background

Relationships between species, genes and genomes have been printed as trees for over a century. Whilst this may have been the best format for exchanging and sharing phylogenetic hypotheses during the 20^th century, the worldwide web now provides faster and automated ways of transferring and sharing phylogenetic knowledge. However, novel software is needed to defrost these published phylogenies for the 21^st century.

Results

TreeRipper is a simple website for the fully-automated recognition of multifurcating phylogenetic trees (http://linnaeus.zoology.gla.ac.uk/~jhughes/treeripper/). The program accepts a range of input image formats (PNG, JPG/JPEG or GIF). The underlying command line c++ program follows a number of cleaning steps to detect lines, remove node labels, patch-up broken lines and corners and detect line edges. The edge contour is then determined to detect the branch length, tip label positions and the topology of the tree. Optical Character Recognition (OCR) is used to convert the tip labels into text with the freely available tesseract-ocr software. 32% of images meeting the prerequisites for TreeRipper were successfully recognised, the largest tree had 115 leaves.

Conclusions

Despite the diversity of ways phylogenies have been illustrated making the design of a fully automated tree recognition software difficult, TreeRipper is a step towards automating the digitization of past phylogenies. We also provide a dataset of 100 tree images and associated tree files for training and/or benchmarking future software. TreeRipper is an open source project licensed under the GNU General Public Licence v3.     

Physiological Correlates of the Big 5: Autonomic Responses to Video Presentations

Personality’s link to emotional experience has been demonstrated, but specific biological responses to emotion as a function of personality have not been well-established. Here, the association between personality and physiological responses (heart rate, skin conductance, and respiration) to emotional videos was assessed. One-hundred sixty-nine participants self-reported on their Big 5 personality traits and underwent ambulatory monitoring as they watched four brief video clips from primetime television content showing scenes containing violence, fear, sadness, and tension. Generally, the negatively-toned emotional scenes provoked increases in skin conductance response and declines in heart rate. We found that physiological outcomes depended on the particular emotional scene and on personality, most notably Extraversion and Neuroticism. Extraversion, and to a lesser degree, Neuroticism, were associated with increases in autonomic arousal responses to the scenes. Gender also interacted with personality to predict responses, such that women who scored higher on measures of Extraversion, Neuroticism, and Conscientious tended to show more physiological arousal than men. Overall, the emotional scenes evoked increases in arousal and more controlled attention. The findings are discussed in context of the limited capacity model and shed light on how personality and gender affect physiological reactions to emotional experiences in everyday life.     

Initial results and long-term clinical follow-up of an amorphous hydrogenated silicon-carbide-coated stent in daily practice

The hemocompatibility and biocompatibility of a stent are determined by the physical and electrochemical properties of the stent surface. The aim of this study was to determine the feasibility, safety and efficacy of implantation of a stent coated with silicon carbide. Baseline characteristics were collected prospectively. The occurrence of cardiac adverse events and the angina score were assessed at clinical follow-up. A total of 193 Tensum stents were implanted in 174 patients. In hospital, one patient experienced stent thrombosis and in 6% of the patients a creatinine kinase elevation to 240 U/l or more occurred. Long-term follow-up was performed in 172 patients, with a mean follow-up of 454 +/- 181 days. Ninety-seven per cent were still alive, 15% had undergone target-vessel revascularization, and 2% had angiographic restenosis and were treated with medication only. Seventy-one per cent of the patients were free of anginal complaints, and 20% had anginal complaints in Canadian Cardiac Society class I or II. The Tensum coronary stent showed to be a safe and efficacious device in this study, with a high primary success rate and favorable long-term clinical followup.     

Human Pumilio Proteins Recruit Multiple Deadenylases to Efficiently Repress Messenger RNAs

PUF proteins are a conserved family of eukaryotic RNA-binding proteins that regulate specific mRNAs: they control many processes including stem cell proliferation, fertility, and memory formation. PUFs repress protein expression from their target mRNAs but the mechanism by which they do so remains unclear, especially for humans. Humans possess two PUF proteins, PUM1 and PUM2, which exhibit similar RNA binding specificities. Here we report new insights into their regulatory activities and mechanisms of action. We developed functional assays to measure sequence-specific repression by PUM1 and PUM2. Both robustly inhibit translation and promote mRNA degradation. Purified PUM complexes were found to contain subunits of the CCR4-NOT (CNOT) complex, which contains multiple enzymes that catalyze mRNA deadenylation. PUMs interact with the CNOT deadenylase subunits in vitro. We used three approaches to determine the importance of deadenylases for PUM repression. First, dominant-negative mutants of CNOT7 and CNOT8 reduced PUM repression. Second, RNA interference depletion of the deadenylases alleviated PUM repression. Third, the poly(A) tail was necessary for maximal PUM repression. These findings demonstrate a conserved mechanism of PUF-mediated repression via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. A second, deadenylation independent mechanism was revealed by the finding that PUMs repress an mRNA that lacks a poly(A) tail. Thus, human PUMs are repressors capable of deadenylation-dependent and -independent modes of repression.     

1Alpha,25-dihydroxyvitamin D3 receptor: competitive binding of vitamin D analogs

The intestinal nuclear receptor for lα,25-dihydroxyvitamin D₃ has been utilized to determine the ability of vitamin D-active sterols to compete with this hormone at the molecular level. 25-Hydroxyvitamin D₃ and lα-hydroxyvitamin D₃ must be present in 150 and 450 times the concentration respectively of lα,25-dihydroxyvitamin D₃, $\text{in}$$\text{vitro}$, to displace the physiologic hormone. These data indicate that: i) superphysiologic levels of 25-hydroxyvitamin D₃ may simulate lα,25-dihydroxyvitamin D₃ and act directly on isolated target organs and ii) the biologic potency observed for low doses of lα-hydroxyvitamin D₃, $\text{in}$$\text{vivo}$, is probably the result of 25-hidroxylation of the lα-derivative to form lα,25-dihydroxyvitamin D₃.     

Historical ecology with real numbers: past and present extent and biomass of an imperilled estuarine habitat

Historic baselines are important in developing our understanding of ecosystems in the face of rapid global change. While a number of studies have sought to determine changes in extent of exploited habitats over historic timescales, few have quantified such changes prior to late twentieth century baselines. Here, we present, to our knowledge, the first ever large-scale quantitative assessment of the extent and biomass of marine habitat-forming species over a 100-year time frame. We examined records of wild native oyster abundance in the United States from a historic, yet already exploited, baseline between 1878 and 1935 (predominantly 1885-1915), and a current baseline between 1968 and 2010 (predominantly 2000-2010). We quantified the extent of oyster grounds in 39 estuaries historically and 51 estuaries from recent times. Data from 24 estuaries allowed comparison of historic to present extent and biomass. We found evidence for a 64 per cent decline in the spatial extent of oyster habitat and an 88 per cent decline in oyster biomass over time. The difference between these two numbers illustrates that current areal extent measures may be masking significant loss of habitat through degradation.     

Effects of chronic exercise on the ultrastructure of the adrenocortical cells in the rat

Summary Four groups of male rats were exercised for periods of 2, 4, 6, and 8 weeks with controls in each group. As a result of chronic exercise there was an increase in the width of the zona fasciculata of the adrenal cortex. Also, there was an increase in the number and size of the mitochondria, and an increase in the quantity of smooth endoplasmic reticulum, and during the first 4 weeks of exercise an increase in the number of lipid droplets in the zona fasciculata. The close relationship between the smooth endoplasmic reticulum and the mitochondria, and the relationship between the smooth endoplasmic reticulum and the lipid droplets suggests a possible means for a transport mechanism for movement of precursors between these organelles.This research was supported in part by a Public Health Research Career Development Award KO4 GM42,355 from the National Institute of General Medical Sciences     

ON THE POSSIBLE FUNCTION OF COATED VESICLES IN MELANOGENESIS OF THE REGENERATING FOWL FEATHER

How tyrosinase becomes associated with the premelanosomes was investigated by histochemical demonstration of tyrosinase activity by the use of dihydroxyphenylalanine (DOPA) in melanocytes of regenerating fowl feathers. The reaction product of DOPA was localized in the anastomosing membrane tubules associated with the concave side of some dictyosomes of the Golgi apparatus and in coated vesicles most of which were in connection with the dictyosomes. No reaction product was found in early premelanosomes. In premelanosomes, the reaction product of DOPA appears first in vesicles approximately 400 A in diameter which are surrounded by a matrix with a characteristic periodicity. These observations seem to allow the speculation that the coated vesicles function in the transport of tyrosinase, and that the premelanosomes are formed in a process which is not necessarily dependent on the Golgi apparatus as was assumed earlier.