A Reversibly Porous Supramolecular Peptide Framework.

The ability to use bio-inspired building-blocks in the assembly of novel supramolecular frameworks is at the forefront of this exciting research field. Herein, we present the first polyproline helix to self-assemble into a reversibly porous, crystalline, supramolecular peptide framework (SPF). This framework is assembled from a short oligoproline, adopting the polyproline II conformation, driven by hydrogen-bonding and dispersion interactions. Thermal activation, guest-induced dynamic porosity and enantioselective guest inclusion have been demonstrated for this novel system. The principles of the self-assembly associated with this SPF will be used as a blueprint allowing for the further development of helical peptide linkers in the rational design of SPFs and metalpeptide frameworks

Belowground DNA-based techniques: untangling the network of plant root interactions

Contains fulltext : 91591.pdf (publisher's version ) (Closed access)7 p

Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe

Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery1,2, spreading efficiently via low-dose fecal-oral transmission3,4. Historically, S. sonnei has been predominantly responsible for dysentery in developed countries, but is now emerging as a problem in the developing world, apparently replacing the more diverse S. flexneri in areas undergoing economic development and improvements in water quality4-6. Classical approaches have shown S. sonnei is genetically conserved and clonal7. We report here whole-genome sequencing of 132 globally-distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and has diversified into several distinct lineages with unique characteristics. Our analysis suggests the majority of this diversification occurred in Europe, followed by more recent establishment of local pathogen populations in other continents predominantly due to the pandemic spread of a single, rapidly-evolving, multidrug resistant lineage

Primary care patients reporting concerns about their gambling frequently have other co-occurring lifestyle and mental health issues

BACKGROUND: Problem gambling often goes undetected by family physicians but may be associated with stress-related medical problems as well as mental disorders and substance abuse. Family physicians are often first in line to identify these problems and to provide a proper referral. The aim of this study was to compare a group of primary care patients who identified concerns with their gambling behavior with the total population of screened patients in relation to co-morbidity of other lifestyle risk factors or mental health issues. METHODS: This is a cross sectional study comparing patients identified as worrying about their gambling behavior with the total screened patient population for co morbidity. The setting was 51 urban and rural New Zealand practices. Participants were consecutive adult patients per practice (N = 2,536) who completed a brief multi-item tool screening primary care patients for lifestyle risk factors and mental health problems (smoking, alcohol and drug misuse, problem gambling, depression, anxiety, abuse, anger). Data analysis used descriptive statistics and non-parametric binomial tests with adjusting for clustering by practitioner using STATA survey analysis. RESULTS: Approximately 3/100 (3%) answered yes to the gambling question. Those worried about gambling more likely to be male OR 1.85 (95% CI 1.1 to 3.1). Increasing age reduced likelihood of gambling concerns – logistic regression for complex survey data OR = 0.99 (CI 95% 0.97 to 0.99) p = 0.04 for each year older. Patients concerned about gambling were significantly more likely (all p < 0.0001) to have concerns about their smoking, use of recreational drugs, and alcohol. Similarly there were more likely to indicate problems with depression, anxiety and anger control. No significant relationship with gambling worries was found for abuse, physical inactivity or weight concerns. Patients expressing concerns about gambling were significantly more likely to want help with smoking, other drug use, depression and anxiety. CONCLUSION: Our questionnaire identifies patients who express a need for help with gambling and other lifestyle and mental health issues. Screening for gambling in primary care has the potential to identify individuals with multiple co-occurring disorders

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer

Background:Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC).Methods:We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety.Results:Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) ⩾8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated.Conclusions:The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC

The 2010 Antarctic ozone hole: Observed reduction in ozone destruction by minor sudden stratospheric warmings

Satellite observations show that the 2010 Antarctic ozone hole is characterized by anomalously small amounts of photochemical ozone destruction (40-60% less than the 2005-2009 average). Observations from the MLS instrument show that this is mainly related to reduced photochemical ozone destruction between 20-25 km altitude. Lower down between 15-20 km the atmospheric chemical composition and photochemical ozone destruction is unaffected. The modified chemical composition and chemistry between 20-25 km altitude in 2010 is related to the occurrence of a mid-winter minor Antarctic Sudden Stratospheric Warming (SSW). The measurements indicate that the changes in chemical composition are related to downward motion of air masses rather than horizontal mixing, and affect stratospheric chemistry for several months. Since 1979, years with similar anomalously small amounts of ozone destruction are all characterized by either minor or major SSWs, illustrating that their presence has been a necessary pre-condition for reduced Antarctic stratospheric ozone destruction

Subglacial lake drainage detected beneath the Greenland ice sheet

The contribution of the Greenland ice sheet to sea-level rise has accelerated in recent decades. Subglacial lake drainage events can induce an ice sheet dynamic response—a process that has been observed in Antarctica, but not yet in Greenland, where the presence of subglacial lakes has only recently been discovered. Here we investigate the water flow paths from a subglacial lake, which drained beneath the Greenland ice sheet in 2011. Our observations suggest that the lake was fed by surface meltwater flowing down a nearby moulin, and that the draining water reached the ice margin via a subglacial tunnel. Interferometric synthetic aperture radar-derived measurements of ice surface motion acquired in 1995 suggest that a similar event may have occurred 16 years earlier, and we propose that, as the climate warms, increasing volumes of surface meltwater routed to the bed will cause such events to become more common in the future

Reconciliation of halogen-induced ozone loss with the total-column ozone record

The observed depletion of the ozone layer from the 1980s onwards is attributed to halogen source gases emitted by human activities. However, the precision of this attribution is complicated by year-to-year variations in meteorology, that is, dynamical variability, and by changes in tropospheric ozone concentrations. As such, key aspects of the total-column ozone record, which combines changes in both tropospheric and stratospheric ozone, remain unexplained, such as the apparent absence of a decline in total-column ozone levels before 1980, and of any long-term decline in total-column ozone levels in the tropics. Here we use a chemistry–climate model to estimate changes in halogen-induced ozone loss between 1960 and 2010; the model is constrained by observed meteorology to remove the effects of dynamical variability, and driven by emissions of tropospheric ozone precursors to separate out changes in tropospheric ozone. We show that halogen-induced ozone loss closely followed stratospheric halogen loading over the studied period. Pronounced enhancements in ozone loss were apparent in both hemispheres following the volcanic eruptions of El Chichon and, in particular, Mount Pinatubo, which significantly enhanced stratospheric aerosol loads. We further show that approximately 40% of the long-term non-volcanic ozone loss occurred before 1980, and that long-term ozone loss also occurred in the tropical stratosphere. Finally, we show that halogen-induced ozone loss has declined by over 10% since stratospheric halogen loading peaked in the late 1990s, indicating that the recovery of the ozone layer is well underway

The management of cancer in the elderly: targeted therapies in oncology

Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described