Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites.

M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with M-CSA are to provide an open data resource for the community to browse known enzyme reaction mechanisms and catalytic sites, and to use the dataset to understand enzyme function and evolution. M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic sites of enzymes. We are releasing M-CSA as a new website and underlying database architecture. At the moment, M-CSA contains 961 entries, 423 of these with detailed mechanism information, and 538 with information on the catalytic site residues only. In total, these cover 81% (195/241) of third level EC numbers with a PDB structure, and 30% (840/2793) of fourth level EC numbers with a PDB structure, out of 6028 in total. By searching for close homologues, we are able to extend M-CSA coverage of PDB and UniProtKB to 51 993 structures and to over five million sequences, respectively, of which about 40% and 30% have a conserved active site

Linking women editors of periodicals to the Wikidata Knowledge Graph

Stories are important tools for recounting and sharing the past. To tell a story one has to put together diverse information about people, places, time periods, and things. We detail here how a machine, through the power of Semantic Web, can compile scattered and diverse materials and information to construct stories. Through the example of the WeChangEd research project on women editors of periodicals in Europe from 1710 – 1920 we detail how to move from archive, to a structured data model and relational database, to a Linked Open Data model and make this information available on Wikidata, to the use of the Stories Services API to generate multimedia stories related to people, organizations and periodicals. This resulted in the WeChangEd Stories App, https://stories.wechanged.ugent.be/

Incidence and Cost of Acute Kidney Injury in Hospitalized Patients with Infective Endocarditis

Acute kidney injury (AKI) is a frequent complication of hospitalized patients with infective endocarditis (IE). Further, AKI in the setting of IE is associated with high morbidity and mortality. We aimed to examine the incidence, clinical parameters, and hospital costs associated with AKI in hospitalized patients with IE in an endemic area with an increasing prevalence of opioid use. This retrospective cohort study included 269 patients admitted to a major referral center in Kentucky with a primary diagnosis of IE from January 2013 to December 2015. Of these, 178 (66.2%) patients had AKI by Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria: 74 (41.6%) had AKI stage 1 and 104 (58.4%) had AKI stage ≥ 2. In multivariable analysis, higher comorbidity scores and the need for diuretics were independently associated with AKI, while the involvement of the tricuspid valve and the need for vasopressor/inotrope support were independently associated with severe AKI (stage ≥ 2). The median total direct cost of hospitalization was progressively higher according to each stage of AKI ($17,069 for no AKI;$37,111 for AKI stage 1; and $61,357 for AKI stage ≥ 2; p \u3c 0.001). In conclusion, two-thirds of patients admitted to the hospital due to IE had incident AKI. The occurrence of AKI significantly increased healthcare costs. The higher level of comorbidity, the affection of the tricuspid valve, and the need for diuretics and/or vasoactive drugs were associated with severe AKI in this susceptible population

A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas

Background Relapsed and refractory sarcomas continue to have poor survival rates. The cancer stem cell (CSC) theory provides a tractable explanation for the observation that recurrences occur despite dramatic responses to upfront chemotherapy. Preclinical studies demonstrated that inhibition of the mechanistic target of rapamycin (mTOR) sensitizes the CSC population to chemotherapy. Methods Here we present the results of the Phase II portion of a Phase I/II clinical trial that aimed to overcome the chemoresistance of sarcoma CSC by combining the mTOR inhibitor temsirolimus (20 mg/m2 weekly) with the chemotherapeutic agent liposomal doxorubicin (30 mg/m2 monthly). Results Fifteen patients with relapsed/refractory sarcoma were evaluable at this recommended Phase 2 dose level. The median progression free survival was 315 days (range 27–799). Response rate, defined as stable disease or better for 60 days, was 53%. Nine of the patients had been previously treated with doxorubicin. Therapy was well tolerated. In a small number of patients, pre- and post- treatment tumor biopsies were available for assessment of ALDH expression as a marker of CSCs and showed a correlation between response and decreased ALDH expression. We also found a correlation between biopsy-proven inhibition of mTOR and response. Conclusions Our study adds to the literature supporting the addition of mTOR inhibition to chemotherapy agents for the treatment of sarcomas, and proposes that a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy may be through sensitizing the chemoresistant CSC population. Further study, ideally with pre- and post-therapy assessment of ALDH expression in tumor cells, is warranted. Trial registration The trial was registered on clinicaltrials.gov (NCT00949325) on 30 July 2009. http://www.editorialmanager.com/csrj/default.asp

Personalised service? Changing the role of the government librarian

Investigates the feasibility of personalised information service in a government department. A qualitative methodology explored stakeholder opinions on the remit, marketing, resourcing and measurement of the service. A questionnaire and interviews gathered experiences of personalised provision across the government sector. Potential users were similarly surveyed to discuss how the service could meet their needs. Data were analysed using coding techniques to identify emerging theory. Lessons learned from government librarians centred on clarifying requirements, balancing workloads and selective marketing. The user survey showed low usage and awareness of existing specialist services, but high levels of need and interest in services repackaged as a tailored offering. Fieldwork confirmed findings from the literature on the scope for adding value through information management advice, information skills training and substantive research assistance and the need to understand business processes and develop effective partnerships. Concluding recommendations focus on service definition, strategic marketing, resource utilisation and performance measurement

Substance use disorders in women with anorexia nervosa

Objective: We examined prevalence of in women substance use disorders (SUID) with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating. Method: Participants (N = 731) were drawn from the international Price Foundation Genetic Studies. Results: The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status. Discussion: SUD are common in AN and are associated with bulimic symptomatology. Results underscore the het-erogeneity in AN, highlighting the importance of screening for SUD across AN subtype

Is season of birth related to disordered eating and personality in women with eating disorders?

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders

Tropical peatlands and their conservation are important in the context of COVID-19 and potential future (zoonotic) disease pandemics.

The COVID-19 pandemic has caused global disruption, with the emergence of this and other pandemics having been linked to habitat encroachment and/or wildlife exploitation. High impacts of COVID-19 are apparent in some countries with large tropical peatland areas, some of which are relatively poorly resourced to tackle disease pandemics. Despite this, no previous investigation has considered tropical peatlands in the context of emerging infectious diseases (EIDs). Here, we review: (i) the potential for future EIDs arising from tropical peatlands; (ii) potential threats to tropical peatland conservation and local communities from COVID-19; and (iii) potential steps to help mitigate these risks. We find that high biodiversity in tropical peat-swamp forests, including presence of many potential vertebrate and invertebrate vectors, combined, in places, with high levels of habitat disruption and wildlife harvesting represent suitable conditions for potential zoonotic EID (re-)emergence. Although impossible to predict precisely, we identify numerous potential threats to tropical peatland conservation and local communities from the COVID-19 pandemic. This includes impacts on public health, with the potential for haze pollution from peatland fires to increase COVID-19 susceptibility a noted concern; and on local economies, livelihoods and food security, where impacts will likely be greater in remote communities with limited/no medical facilities that depend heavily on external trade. Research, training, education, conservation and restoration activities are also being affected, particularly those involving physical groupings and international travel, some of which may result in increased habitat encroachment, wildlife harvesting or fire, and may therefore precipitate longer-term negative impacts, including those relating to disease pandemics. We conclude that sustainable management of tropical peatlands and their wildlife is important for mitigating impacts of the COVID-19 pandemic, and reducing the potential for future zoonotic EID emergence and severity, thus strengthening arguments for their conservation and restoration. To support this, we list seven specific recommendations relating to sustainable management of tropical peatlands in the context of COVID-19/disease pandemics, plus mitigating the current impacts of COVID-19 and reducing potential future zoonotic EID risk in these localities. Our discussion and many of the issues raised should also be relevant for non-tropical peatland areas and in relation to other (pandemic-related) sudden socio-economic shocks that may occur in future

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution