Showing papers by "University of Liverpool published in 2012"
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
11,809 citations
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
9,324 citations
TL;DR: In this article, a search for the Standard Model Higgs boson in proton-proton collisions with the ATLAS detector at the LHC is presented, which has a significance of 5.9 standard deviations, corresponding to a background fluctuation probability of 1.7×10−9.
9,282 citations
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
6,861 citations
Daniel J. Klionsky1, Fábio Camargo Abdalla2, Hagai Abeliovich3, Robert T. Abraham4 +1284 more•Institutions (463)
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
4,316 citations
TL;DR: It is shown that childhood adversity is strongly associated with increased risk for psychosis and population attributable risk was 33% (16%–47%).
Abstract: Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.
1,893 citations
TL;DR: High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10–deficient (Il10−/−) mice, suggesting that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.
Abstract: Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10-deficient (Il10(-/-)) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)-treated Il10(-/-) mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10(-/-) mice, without altering intestinal inflammation. Mucosa-associated pks(+) E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.
1,720 citations
TL;DR: Examining the mutational spectra of Ras isoforms curated from large-scale tumor profiling found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases, which were unexpected given that these mutations occur in regions that share 100% amino- acid sequence identity among the 3 isoforms.
Abstract: All mammalian cells express three closely related Ras proteins: H-Ras, K-Ras and N-Ras that promote oncogenesis when mutationally activated at codons 12, 13 or 61. Despite a high degree of similarity between the isoforms, K-Ras mutations are far more frequently observed in cancer and each isoform displays preferential coupling to particular cancer types. We have examined the mutation spectra of Ras isoforms curated from large-scale tumour profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino acid substitution biases. These were unexpected given that these mutations occur in regions that share 100% amino acid sequence identity between the three isoforms. Importantly, many of the mutational biases were not due to differences in exposure to mutagens because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms together with isoform-specific differences in protein structure and signalling that may promote these distinct mutation patterns and differential coupling to specific cancers.
1,598 citations
TL;DR: The need for general guidance on the development of core outcome sets, which should be measured and reported, as a minimum, in all trials for a specific clinical area, is identified.
Abstract: The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus.
1,215 citations
TL;DR: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.
Abstract: OBJECTIVE: To review the evidence about the prevalence and determinants of non-psychotic common perinatal mental disorders (CPMDs) in World Bank categorized low- and lower-middle-income countries. METHODS: Major databases were searched systematically for English-language publications on the prevalence of non-psychotic CPMDs and on their risk factors and determinants. All study designs were included. FINDINGS: Thirteen papers covering 17 low- and lower-middle-income countries provided findings for pregnant women, and 34, for women who had just given birth. Data on disorders in the antenatal period were available for 9 (8%) countries, and on disorders in the postnatal period, for 17 (15%). Weighted mean prevalence was 15.6% (95% confidence interval, CI: 15.4-15.9) antenatally and 19.8% (19.5-20.0) postnatally. Risk factors were: socioeconomic disadvantage (odds ratio [OR] range: 2.1-13.2); unintended pregnancy (1.6-8.8); being younger (2.1-5.4); being unmarried (3.4-5.8); lacking intimate partner empathy and support (2.0-9.4); having hostile in-laws (2.1-4.4); experiencing intimate partner violence (2.11-6.75); having insufficient emotional and practical support (2.8-6.1); in some settings, giving birth to a female (1.8-2.6), and having a history of mental health problems (5.1-5.6). Protective factors were: having more education (relative risk: 0.5; P = 0.03); having a permanent job (OR: 0.64; 95% CI: 0.4-1.0); being of the ethnic majority (OR: 0.2; 95% CI: 0.1-0.8) and having a kind, trustworthy intimate partner (OR: 0.52; 95% CI: 0.3-0.9). CONCLUSION: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.
University of Cologne1, Max Planck Society2, University of Bonn3, Ghent University4, Broad Institute5, Stanford University6, Technical University of Dortmund7, Columbia University8, University of Melbourne9, St. Vincent's Health System10, University of Jena11, Casa Sollievo della Sofferenza12, University of Groningen13, VU University Amsterdam14, University of Bologna15, University of Liverpool16, University of Oslo17, University of Zurich18, Peter MacCallum Cancer Centre19, Institut Gustave Roussy20, University of Grenoble21, Vanderbilt University22, Harvard University23, University of Washington24, University of Strasbourg25
TL;DR: This study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
Abstract: Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice(4). Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.
TL;DR: In this article, the authors focused on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. But they did not consider the risk of pregnancy complications.
TL;DR: It is shown that the hexaploid genome is highly dynamic, with significant loss of gene family members on polyploidization and domestication, and an abundance of gene fragments.
Abstract: Bread wheat (Triticum aestivum) is a globally important crop, accounting for 20 per cent of the calories consumed by humans. Major efforts are underway worldwide to increase wheat production by extending genetic diversity and analysing key traits, and genomic resources can accelerate progress. But so far the very large size and polyploid complexity of the bread wheat genome have been substantial barriers to genome analysis. Here we report the sequencing of its large, 17-gigabase-pair, hexaploid genome using 454 pyrosequencing, and comparison of this with the sequences of diploid ancestral and progenitor genomes. We identified between 94,000 and 96,000 genes, and assigned two-thirds to the three component genomes (A, B and D) of hexaploid wheat. High-resolution synteny maps identified many small disruptions to conserved gene order. We show that the hexaploid genome is highly dynamic, with significant loss of gene family members on polyploidization and domestication, and an abundance of gene fragments. Several classes of genes involved in energy harvesting, metabolism and growth are among expanded gene families that could be associated with crop productivity. Our analyses, coupled with the identification of extensive genetic variation, provide a resource for accelerating gene discovery and improving this major crop.
University of Cologne1, Misericordia University2, University Hospital of Lausanne3, Radboud University Nijmegen Medical Centre4, Necker-Enfants Malades Hospital5, Pasteur Institute6, Katholieke Universiteit Leuven7, Hacettepe University8, Statens Serum Institut9, Boston Children's Hospital10, Carlos III Health Institute11, University of Strasbourg12, University of Liverpool13, University of Copenhagen14, Innsbruck Medical University15, National and Kapodistrian University of Athens16, Manchester Academic Health Science Centre17, University of Genoa18, University of Würzburg19
TL;DR: This part of the EFISG guidelines focuses on non-neutropenic adult patients, and liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength for the targeted initial treatment of candidaemia.
TL;DR: The use of nanoporous organic polymers for applications such as catalysis and separations is an important developing area, and recent developments as well as highlighting potential future opportunities are discussed in this article.
TL;DR: In this paper, a cross sectional TEM view of several graphene and boron nitride heterostructures is presented, showing that the trapped hydrocarbons segregate into isolated pockets, leaving the interfaces atomically clean.
Abstract: Heterostructures of very thin films have been used for decades in research and industry. Now a transmission electron microscopy study demonstrates the possibility of realizing perfect structures built by piling up one-atom-thick layers of graphene and boron nitride. By stacking various two-dimensional (2D) atomic crystals1 on top of each other, it is possible to create multilayer heterostructures and devices with designed electronic properties2,3,4,5. However, various adsorbates become trapped between layers during their assembly, and this not only affects the resulting quality but also prevents the formation of a true artificial layered crystal upheld by van der Waals interaction, creating instead a laminate glued together by contamination. Transmission electron microscopy (TEM) has shown that graphene and boron nitride monolayers, the two best characterized 2D crystals, are densely covered with hydrocarbons (even after thermal annealing in high vacuum) and exhibit only small clean patches suitable for atomic resolution imaging6,7,8,9,10. This observation seems detrimental for any realistic prospect of creating van der Waals materials and heterostructures with atomically sharp interfaces. Here we employ cross sectional TEM to take a side view of several graphene–boron nitride heterostructures. We find that the trapped hydrocarbons segregate into isolated pockets, leaving the interfaces atomically clean. Moreover, we observe a clear correlation between interface roughness and the electronic quality of encapsulated graphene. This work proves the concept of heterostructures assembled with atomic layer precision and provides their first TEM images.
TL;DR: Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20–25% and might have adapted to cause invasive disease in human beings.
TL;DR: The comparison of visual acuity at 1 year between bevacizumab and ranibizumabs was inconclusive, and other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.
University of Barcelona1, Research Triangle Park2, University of Nebraska Medical Center3, University of Edinburgh4, GlaxoSmithKline5, University of Copenhagen6, University of Manchester7, University of Cambridge8, University of Liverpool9, Maastricht University10, Brigham and Women's Hospital11, University of British Columbia12, University of Bergen13
TL;DR: Overall, the results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment and show associations but do not prove causality.
Abstract: Background: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). Methods and Findings: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-a levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 nonsmoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p,0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p,0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice. Conclusions: Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
TL;DR: Results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.
Abstract: The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.
Wellcome Trust Sanger Institute1, Massachusetts Institute of Technology2, University of Cambridge3, University of Edinburgh4, National Research Council5, National Institutes of Health6, Liverpool School of Tropical Medicine7, University of Liverpool8, Harvard University9, University College London10
TL;DR: Data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.
Abstract: The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.
TL;DR: This article showed that the percentage of the total phytoplankton biovolume attributable to cyanobacteria increases steeply with temperature, indicating a synergistic effect of nutrients and climate.
Abstract: Dominance by cyanobacteria hampers human use of lakes and reservoirs worldwide. Previous studies indicate that excessive nutrient loading and warmer conditions promote dominance by cyanobacteria, but evidence from global scale field data has so far been scarce. Our analysis, based on a study of 143 lakes along a latitudinal transect ranging from subarctic Europe to southern South America, shows that although warmer climates do not result in higher overall phytoplankton biomass, the percentage of the total phytoplankton biovolume attributable to cyanobacteria increases steeply with temperature. Our results also reveal that the percent cyanobacteria is greater in lakes with high rates of light absorption. This points to a positive feedback because restriction of light availability is often a consequence of high phytoplankton biovolume, which in turn may be driven by nutrient loading. Our results indicate a synergistic effect of nutrients and climate. The implications are that in a future warmer climate, nutrient concentrations may have to be reduced substantially from present values in many lakes if cyanobacterial dominance is to be controlled.
TL;DR: Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin and establishes through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.
Abstract: Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding. Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components. Design and Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries. Patients: Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin. Intervention: Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk. Main Outcome Measures: Primary endpoint w...
TL;DR: In this article, the BaBar data sample was used to investigate the sensitivity of BaBar ratios to new physics contributions in the form of a charged Higgs boson in the type II two-Higgs doublet model.
Abstract: Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.
World Organisation for Animal Health1, EcoHealth Alliance2, International Union for Conservation of Nature and Natural Resources3, Santa Fe Institute4, Princeton University5, National Institutes of Health6, University of California, Los Angeles7, Food and Agriculture Organization8, Chatham House9, University of Liverpool10, United States Department of Health and Human Services11, University of London12
TL;DR: This work aimed to review how zoonotic diseases result from natural pathogen ecology, and how other circumstances, such as animal production, extraction of natural resources, and antimicrobial application change the dynamics of disease exposure to human beings.
TL;DR: A waterstable porous porphyrin MOF with a BET surface area of 1400 m g 1 which performs visible-lightdriven hydrogen generation from water and reveals that no aluminium is coordinated within the porphyrsin ring, consistent with the need to use reactive trialkylaluminium reagents for metalation of the p Morphyrin in solution.
Abstract: Metal–organic frameworks (MOFs) permit the combination of high internal surface area with chemical and physical functionality conferred by the molecular linker. Porphyrins are versatile functional molecules in catalysis, light harvesting, and molecular sensing. Porphyrins have been used as building blocks for MOFs, affording catalysts, light harvesting and selective sorption in liquid and gas phases. MOFs based on Alcarboxylate coordination chemistry are amongst the most thermally and chemically stable of such systems reported to date. Here we report a waterstable porous porphyrin MOF with a BET surface area of 1400 m g 1 which performs visible-lightdriven hydrogen generation from water. The freebase porphyrin can be metalated within the rigid host structure. The reaction of AlCl3·6 H2O with the free-base meso-tetra(4-carboxyl-phenyl) porphyrin H2TCPP (Figure 1b) in water under hydrothermal conditions at 180 8C followed by washing with dimethyl formamide (DMF) to remove unreacted ligand leads to the formation of the microcrystalline porous red compound H2TCPP[AlOH]2(DMF3(H2O)2) 1 (referred to as Al-PMOF, experimental details are given in section 1.1 in the Supporting Information). The linker consists of four benzoate groups around the central porphyrin core. The analyzed composition reveals that no aluminium is coordinated within the porphyrin ring, consistent with the need to use reactive trialkylaluminium reagents for metalation of the porphyrin in solution. The reaction temperature is required to solubilize the porphyrin linker. The crystal structure of 1 was solved and refined from synchrotron powder Xray diffraction collected at 100 K. Indexing and Pawley refinement revealed an orthorhombic cell (a = 31.978(3) , b = 6.5812(4) , c = 16.862(2) , V= 3548.7(6) ) consistent with the C222, Cmm2, and Cmmm space groups. Each of these candidate space groups was evaluated by simulated annealing using a semi-rigid body to describe the TCPP unit (Figure S1 in the Supporting Information) with eight refined parameters describing distances and angles within the porphyrin. The best results were obtained for the benzoic acid group perpendicular to the central porphyrin ring, which can be best described in Cmmm symmetry, and zero occupancy for Al at the center of the porphyrin. This model was used in the final Rietveld analysis (Figure 1a). Fourier mapping revealed a single guest atom in the channels attributed to oxygen from water, which was included in the final refinement (Figure S2 in the Supporting Information). Each porphyrin linker in 1 is coordinated to eight aluminium centers (Figure 1c–e) through the four carboxylate groups which each bridge two aluminium units. There is Figure 1. a) Final Rietveld refinement of 1 (100 K) showing observed (gray crosses), calculated (line a), and difference (line b) plots (Q = 2p/d). Bragg peak positions are indicated. b) TCPP porphyrinic linker in 1. c–e) Crystal structure of 1 viewed down [001], [100], and [010] directions, respectively.
TL;DR: Porous, fluorescent, covalent triazine-based frameworks (CTFs) are obtained in an unprecedentedly mild reaction, opening up a scalable pathway for molecular building blocks previously thought incompatible with this chemistry.
Abstract: Porous, fluorescent, covalent triazine-based frameworks (CTFs) are obtained in an unprecedentedly mild reaction, opening up a scalable pathway for molecular building blocks previously thought incompatible with this chemistry. Choice of monomers and synthetic conditions determines the optical properties and nano-scale ordering of these highly microporous materials with BET surface areas exceeding 1100 m(2) g(-1) and exceptional CO(2) capacities (up to 4.17 mmol g(-1)).
TL;DR: A combined search for the Standard Model Higgs boson with the ATLAS experiment at the LHC using datasets corresponding to integrated luminosities from 1.04 fb(-1) to 4.9 fb(1) of pp collisions is described in this paper.
TL;DR: HMGB1 orchestrates leukocyte recruitment and their induction to secrete inflammatory cytokines by switching between mutually exclusive redox states.
Abstract: Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to sulfonates by reactive oxygen species abrogates both activities. We show that leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1 mutant in which serines replace all cysteines (3S-HMGB1) does not promote cytokine production, but is more effective than wild-type HMGB1 in recruiting leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte recruitment but not with activation. We detected the different redox forms of HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states.