A congruent molecular signature of vicariance across multiple plant lineages

Explaining disjunct distributions, or why closely related organisms are often separated by apparently severe barriers such as oceans or deserts, is a great challenge for historical biogeography. Competing explanations are long-distance dispersal across

Relationships among felt scale insects (Hemiptera:Coccoidea:Eriococcidae) of southern beech, Nothofagus (Nothofagaceae), with the first descriptions of Australian species of the Nothofagus -feeding genus Madarococcus Hoy

Species of southern beech (Nothofagus) have been studied extensively because of their importance in understanding southern hemisphere biogeography. Nothofagus species support a diverse assemblage of insect herbivores, including more than 30 described species of felt scales (Eriococcidae). We reconstructed the phylogeny of the Nothofagus-feeding felt scales with nucleotide sequence data and morphology. All but one of the exclusively Nothofagus-feeding species included in the analyses were recovered as a monophyletic group. This clade comprised the genera Chilechiton Hodgson & Miller, Chilecoccus Miller & González, Intecticoccus Kondo, Madarococcus Hoy (except for M. totorae Hoy), Sisyrococcus Hoy and several species of the genus Eriococcus Targioni Tozzetti. The genera Eriococcus and Madarococcus were not recovered as monophyletic. Here we revise Madarococcus. We expand the concept of the genus, provide a key to the adult females of the 31 species of Madarococcus and, for each named species, provide revised synonymies and any new collection or taxonomic information. We recognise the genus from Australia for the first time and describe the adult females of six new Australian species: Madarococcus cunninghamii Hardy & Gullan, sp. nov.; M. meander Hardy & Gullan, sp. nov.; M. megaventris Hardy & Gullan, sp. nov.; M. moorei Hardy & Gullan, sp. nov.; M. occultus Hardy & Gullan, sp. nov., and M. osculus Hardy & Gullan, sp. nov. We also describe the first-instar nymphs of M. cunninghamii, sp. nov., M. meander, sp. nov. and M. moorei, sp. nov. We transfer 17 species into Madarococcus from Eriococcus: M. argentifagi (Hoy), comb. nov.; M. cavellii (Maskell), comb. nov.; M. chilensis (Miller & González), comb. nov.; M. detectus (Hoy), comb. nov.; M. eurythrix (Miller & González), comb. nov.; M. fagicorticis (Maskell), comb. nov.; M. hispidus (Hoy), comb. nov.; M. latilobatus (Hoy), comb. nov.; M. maskelli, (Hoy), comb. nov.; M. montifagi (Hoy), comb. nov.; M. navarinoensis (Miller & González), comb. nov.; M. nelsonensis (Hoy), comb. nov.; M. nothofagi (Hoy), comb. nov.; M. podocarpi (Hoy), comb. nov.; M. raithbyi (Maskell), comb. nov.; M. rotundus (Hoy), comb. nov. and M. rubrifagi (Hoy), comb. nov. We transfer two species from Sisyrococcus into Madarococcus: M. intermedius (Maskell), comb. nov. and M. papillosus (Hoy), comb. nov. One species, M. totarae (Maskell), is excluded from Madarococcus, but cannot at present be placed in another genus and is listed as 'M.' totarae incertae sedis. We report the first collection of an eriococcid, M. osculus, sp. nov., on the deciduous beech, Nothofagus gunnii. With respect to biogeography, the results of our phylogenetic analysis are congruent with those obtained from recent analysis of Nothofagus; Australian and New Zealand species of Madarococcus form a monophyletic group to the exclusion of the South American species, suggesting that long-distance dispersal has played an important role in shaping the distributions of both the Nothofagus-feeding felt scales and their hosts

Body and Disease 2008: An Integrated Course Teaching Pathology, Pharmacology, Immunology and Microbiology

The Duke-NUS Graduate Medical School Singapore (Duke-NUS) Body and Disease course is a 20-week, integrated course occurring at the end of the first year. The course covers four basic science topics: Pathology, Pharmacology, Immunology, and Microbiology and is modelled after the same course from the Duke University School of Medicine (DSOM) in Durham, North Carolina, USA. The structure of the course, as delivered by DSOM, was adapted to meet the needs and structure of the Duke-NUS programme. In addition, the course was adapted significantly to incorporate the Team-Based Learning methodology. In this paper, we detail how we approached these unique challenges. This paper presents an overview of the course structure, preliminary evaluation, and implications for future implementation

Species delimitation in asexual insects of economic importance: The case of black scale (Parasaissetia nigra), a cosmopolitan parthenogenetic pest scale insect

Asexual lineages provide a challenge to species delimitation because species concepts either have little biological meaning for them or are arbitrary, since every individual is monophyletic and reproductively isolated from all other individuals. However, recognition and naming of asexual species is important to conservation and economic applications. Some scale insects are widespread and polyphagous pests of plants, and several species have been found to comprise cryptic species complexes. Parasaissetia nigra (Nietner, 1861) (Hemiptera: Coccidae) is a parthenogenetic, cosmopolitan and polyphagous pest that feeds on plant species from more than 80 families. Here, we implement multiple approaches to assess the species status of P. nigra, including coalescence-based analyses of mitochondrial and nuclear genes, and ecological niche modelling. Our results indicate that the sampled specimens of P. nigra should be considered to comprise at least two ecotypes (or "species") that are ecologically differentiated, particularly in relation to temperature and moisture. The presence of more than one ecotype under the current concept of P. nigra has implications for biosecurity because the geographic extent of each type is not fully known: some countries may currently have only one of the biotypes. Introduction of additional lineages could expand the geographic extent of damage by the pest in some countries.This project was supported, in part, by an Australian Research Council Discovery Projects grant (DP130101141) and funding from The University of Queensland, Australia to LGC, and the College of Life Science, Shanxi University, China to YPL (National Serial Number of Postdoctoral Fellowship: 140975)

Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

BACKGROUND: Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. METHODS: We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. RESULTS: In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular density within the tumors. By contrast, transient exogenous treatment of MDA-MB-231 xenografts with rhSulf2 was not sufficient to inhibit or reverse tumor growth. CONCLUSION: These data indicate that in vivo progression of human breast cancer xenografts can be inhibited with sulfatase expression, and therapeutic effect requires constant delivery at the tumor site. Our results support a direct effect of sulfatases on tumor growth or invasion, rather than an effect in the stromal compartment

Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients

Preventing Violence in Seven Countries: Global Convergence in Policies

Do governments take the measures that are supported by the best scientific evidence available? We present a brief review of the situation in: Australia, Canada, Germany, the Netherlands, Spain, the United Kingdom, and the United States. Our findings show surprisingly similar developments across countries. While all seven countries are moving towards evidence-based decision making regarding policies and programs to prevent violence, there remain a number of difficulties before this end can be achieved. For example, there continue to be few randomized controlled trials or rigorous quasi-experimental studies on aggression and violence. Results from experimental research are essential to both policy makers and researchers to determine the effectiveness of programs as well as increase our knowledge of the problem. Additionally, all noted that media attention for violence is high in their country, often leading to management by crisis with the result that policies are not based on evidence, but instead seek to appease public outrage. And perhaps because of attendant organizational problems (i.e., in many countries violence prevention was not under the guise of one particular agency or ministry), most have not developed a coordinated policy focusing on the prevention of violence and physical aggression. It is hypothesized that leaders in democratic countries, who must run for election every 4 to 6 years, may feel a need to focus on short-term planning rather than long-term preventive policies since the costs, but not the benefits for the latter would be incurred while they still served in office. We also noted a general absence of expertise beyond those within scientific circles. The need for these ideas to be more widely accepted will be an essential ingredient to real and sustaining change. This means that there must be better communication and increased understanding between researchers and policy makers. Toward those ends, the recent establishment of the Campbell Collaboration, formed to provide international systematic reviews of program effectiveness, will make these results more available and accessible to politicians, administrators and those charged with making key policy decision

Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients

BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining β cells in patients with newly diagnosed T1D

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely