Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Chameleon radiation by oceanic dispersal

Historical biogeography is dominated by vicariance methods that search for a congruent pattern of fragmentation of ancestral distributions produced by shared Earth history(1-3). A focus of vicariant studies has been austral area relationships and the break-up of the supercontinent Gondwana(3-5). Chameleons are one of the few extant terrestrial vertebrates thought to have biogeographic patterns that are congruent with the Gondwanan break-up of Madagascar and Africa(6,7). Here we show, using molecular and morphological evidence for 52 chameleon taxa, support for a phylogeny and area cladogram that does not fit a simple vicariant history. Oceanic dispersal-not Gondwanan breakup-facilitated species radiation, and the most parsimonious biogeographic hypothesis supports a Madagascan origin for chameleons, with multiple 'out-of-Madagascar' dispersal events to Africa, the Seychelles, the Comoros archipelago, and possibly Reunion Island. Although dispersal is evident in other Indian Ocean terrestrial animal groups(8-16), our study finds substantial out-of-Madagascar species radiation, and further highlights the importance of oceanic dispersal as a potential precursor for speciation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62614/1/415784a.pd

Real-time algorithm for changes detection in depth of anesthesia signals

This paper presents a real-time algorithm for changes detection in depth of anesthesia signals. A Page-Hinkley test (PHT) with a forgetting mechanism (PHT-FM) was developed. The samples are weighted according to their "age" so that more importance is given to recent samples. This enables the detection of the changes with less time delay than if no forgetting factor was used. The performance of the PHT-FM was evaluated in a two-fold approach. First, the algorithm was run offline in depth of anesthesia (DoA) signals previously collected during general anesthesia, allowing the adjustment of the forgetting mechanism. Second, the PHT-FM was embedded in a real-time software and its performance was validated online in the surgery room. This was performed by asking the clinician to classify in real-time the changes as true positives, false positives or false negatives. The results show that 69 % of the changes were classified as true positives, 26 % as false positives, and 5 % as false negatives. The true positives were also synchronized with changes in the hypnotic or analgesic rates made by the clinician. The contribution of this work has a high impact in the clinical practice since the PHT-FM alerts the clinician for changes in the anesthetic state of the patient, allowing a more prompt action. The results encourage the inclusion of the proposed PHT-FM in a real-time decision support system for routine use in the clinical practice. © 2012 Springer-Verlag

Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

<p>Abstract</p> <p>Background</p> <p>Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H₄receptor (H₄R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H₄R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined.</p> <p>Methods</p> <p>Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H₄R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis.</p> <p>Results</p> <p>Therapeutic H₄R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H₄R antagonist also improved measures of central and peripheral airway dysfunction.</p> <p>Conclusions</p> <p>These data demonstrate that therapeutic H₄R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H₄R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.</p

Phosphorylation-Independent Regulation of Atf1-Promoted Meiotic Recombination by Stress-Activated, p38 Kinase Spc1 of Fission Yeast

BACKGROUND:Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. METHODOLOGY/PRINCIPAL FINDINGS:We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. CONCLUSIONS/SIGNIFICANCE:The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study

BACKGROUND: The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. METHODS: We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. RESULTS: All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. CONCLUSIONS: The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia

Arginine deficiency augments inflammatory mediator production by airway epithelial cells in vitro

<p>Abstract</p> <p>Background</p> <p>Previously we showed that reduced availability of the essential amino acid tryptophan per se attenuates post-transcriptional control of interleukin (IL)-6 and IL-8 leading to hyperresponsive production of these inflammatory mediators by airway epithelial cells. Availability of the non-essential amino acid arginine in the inflamed airway mucosa of patients with asthma is reduced markedly, but it is not known whether this can also lead to an exaggerated production of IL-6 and IL-8.</p> <p>Methods</p> <p>IL-6 and IL-8 were determined by ELISA in culture supernatants of NCI-H292 airway epithelial-like cells and normal bronchial epithelial (NHBE) cells that were exposed to TNF-α, LPS or no stimulus, in medium with or without arginine. Arginine deficiency may also result from exposure to poly-L-arginine or major basic protein (MBP), which can block arginine uptake. Epithelial cells were exposed to these polycationic proteins and L-¹⁴C-arginine uptake was assessed as well as IL-6 and IL-8 production. To determine the mode of action, IL-6 and IL-8 mRNA profiles over time were assessed as were gene transcription and post-transcriptional mRNA degradation.</p> <p>Results</p> <p>For both NCI-H292 and NHBE cells, low arginine concentrations enhanced basal epithelial IL-6 and IL-8 production and synergized with TNF-α-induced IL-6 and IL-8 production. Poly-L-arginine enhanced the stimulus-induced IL-6 and IL-8 production, however, blocking arginine uptake and the enhanced IL-6 and IL-8 production appeared unrelated. The exaggerated IL-6 and IL-8 production due to arginine deficiency and to poly-L-arginine depend on a post-transcriptional and a transcriptional process, respectively.</p> <p>Conclusion</p> <p>We conclude that both reduced arginine availability per se and the presence of polycationic proteins may promote airway inflammation by enhanced pro-inflammatory mediator production in airway epithelial cells, but due to distinct mechanisms.</p

Does Choose & Book fail to deliver the expected choice to patients? A survey of patients' experience of outpatient appointment booking

Provisional abstract: Background: Choose and Book is a central part of the UK Government patient choice agenda that seeks to provide patients with a choice over the time, date and place of their first outpatient appointment. This is done through the use of a computerised booking system. After a 2004 pilot study, Choose and Book was formally launched in January 2006. This is the first study of patient experience of Choose and Book since then. Methods: A questionnaire survey of reported experience of choice over the time, data and place of appointment, carried out in a National Health Service hospital in London. 104 patients at their first outpatient appointment completed the questionnaire, consisting of a consecutive series of patients referred through Choose and Book and a sample referred through the conventional booking system. Results: Among the Choose and Book patients, 66% (31/47; 95% CI 52 to 78%) reported not being given a choice of appointment date, 66% (31/47; 95% CI 52 to 78%) reported not being given a choice of appointment time, 86% (37/43; 95% CI 74 to 94%) reported being given a choice of fewer than four hospitals in total and 32% (15/47; 95% CI 20 to 46%) reported not being given any choice of hospital. Conclusions: In this study, patients did not experience the degree of choice that Choose and Book was designed to deliver

A strategy to obtain axenic cultures of Arthrospira spp. cyanobacteria

A strategy to obtain axenic cultures of the cyanobacterium Arthrospira sp. (‘platensis’) Lefevre 1963/M-132-1 strain, consisting of a series of physical and chemical procedures, and the application of an optimized pool of antibiotics, is described in this paper. This strategy, which is an inexpensive and fast way to obtain axenic cultures, can be applied to Arthrospira spp. from culture collections or samples from their natural habitats to eliminate a wide spectrum of contaminants. A high alkaline treatment (pH 12, using KOH) of 72 h is a determinant initial procedure applied to eliminate protozoa and Microcystis sp. Bacteria were eliminated by an optimal antibiotic pool treatment, and Chroococcus sp. residuals were discarded by serial dilution. Optimal concentrations of the antibiotics composing the pool were obtained by a 24 factorial central composite rotatable design (CCRD) and Response Surface Methodology (RSM), resulting in: ampicillin 61.6 μg/ml, penicillin 85.8 μg/ml, cefoxitin 76.9 μg/ml, and meropenem 38.9 μg/ml. The results also indicate that cefoxitin was the most effective antibiotic of this pool. After obtaining the axenic culture, identification of Lefevre 1963/M-132-1 strain was performed using amplification and sequencing of the ITS region (including part of 16S rRNA, tRNA Ile, ITS, tRNA Ala and part of 23S rRNA region) and fatty acid composition data. Data base comparison revealed that Lefevre strain is closely related to A. platensis species (99% identity), while fatty acid composition data suggested A. maxima. These seemingly contradictory results are discussed