Quality interoperability within digital libraries: the DL.org perspective

Quality is the most dynamic aspect of DLs, and becomes even more complex with respect to interoperability. This paper formalizes the research motivations and hypotheses on quality interoperability conducted by the Quality Working Group within the EU-funded project DL.org (<a href="http://www.dlorg.eu">http://www.dlorg.eu/</a>). After providing a multi-level interoperability framework – adopted by DL.org - the authors illustrate key-research points and approaches on the way to the interoperability of DLs quality, grounding them in the DELOS Reference Model. By applying the DELOS Reference Model Quality Concept Map to their interoperability motivating scenario, the authors subsequently present the two main research outcomes of their investigation - the Quality Core Model and the Quality Interoperability Survey

Pharmacokinetic profiles of the active metamizole metabolites in healthy horses

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 9 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC-UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0-last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0-last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug

HIV-associated progressive multifocal leukoencephalopathy. Current perspectives

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, caused by the polyomavirus JC and occurring almost exclusively in the context of severe immune depression. AIDS represents the most common predisposing condition for PML development. Antiretroviral treatment has reduced PML incidence in HIV-infected subjects, but the disease remains a severe and life-threatening complication of AIDS, considering thus far the lack of an effective anti-JC virus (JCV) direct-acting antiviral drug. In the last decade, the use of monoclonal antibodies for treating immune-based diseases evidenced new predisposing conditions for PML development, promoting a renewed interest in PML pathogenesis. In this article, we review the current knowledge on JCV epidemiology and AIDS-associated PML incidence, JCV viral cycle, pathogenesis, and the interplay with HIV infection. We give an updated overview of diagnostic and prognostic tools available for PML diagnosis and describe past and current therapeutic approaches, including new strategies for PML cure

European ornithomimosaurs (Dinosauria, Theropoda) : an undetected record

Early Cretaceous ornithomimosaurian theropod dinosaurs have been reported from various localities in Asia, whereas they remain poorly represented and extremely rare in North America, Africa and Europe. So far, the only known European ornithomimosaur is Pelecanimimus from the Barremian of Spain. The recent discovery in southwestern France of a lignitic bone bed in Angeac, which has yielded several hundred ornithomimosaur bones, sheds new light on the ornithomimosaurian fossil record. Based on this new material, we re-evaluate here the systematic position of various isolated theropod bones from the Wealden of England, including historical taxa of uncertain affinities. Based on a unique combination of derived characters, Thecocoelurus and Valdoraptor are linked to the Angeac taxon but are considered to be nomina dubia. Valdoraptor from the Valanginian of West Sussex appears to be the oldest known ornithomimosaur together with the contemporaneous Nqwebasaurus from South Africa. Ornithomimosaurs were a common component of the Early Cretaceous European dinosaur fauna. Their presence in Spain, France and England further strengthens the palaeobiogeographic affinities of the European fossil biota with that of Asia during this period

Progetto di alternanza scuola-lavoro per la valorizzazione di collezioni zoologiche

Il progetto si è posto l’obiettivo di implementare le competenze trasversali degli studenti nell’ambito della divulgazione scientifica, attraverso un percorso avviato con lo studio della zoologia e proseguito con attività di comunicazione e guida museale, mantenendo uno spirito collaborativo tra i tutor, il personale del Museo e i giovani. Nel contesto museale, dove un elevato numero di forme animali è concentrato in uno spazio ristretto, gli studenti hanno “toccato con mano” la varietà di specie esistenti, percepita in maniera immediata ed emotivamente significativa. Hanno così imparato ad applicare le metodologie per classificare gli animali e denominarli, integrando, in diversi momenti, l’uso della lingua inglese. Gli studenti hanno poi trasferito praticamente i contenuti acquisiti in un lavoro di ideazione, progettazione e realizzazione di prodotti didattico-divulgativi, presentati in un evento di grande impatto sul territorio della città di Palermo: la “Notte europea dei musei” 2018

Natural product coumarins that inhibit human carbonic anhydrases.

Natural products (NPs) have proven to be an invaluable source of new chemotherapies yet very few have been explored to source small molecule carbonic anhydrase (CA) inhibitors. CA enzymes underpin physiological pH and are critical to the progression of several diseases including cancer. The present study is the first to more widely investigate NP coumarins for CA inhibition following the recent discovery of a NP coumarin CA inhibitor. We assembled a NP library comprising 24 plant coumarins (compounds 4-27) and three ascidian coumarins (compounds 28-30) that together provide a diverse collection of structures containing the coumarin pharmacophore. This library was then evaluated for inhibition of six human CA isozymes (CAs I, II, VII, IX, XII and XIII) and a broad range of inhibition and isozyme selectivity profiles were evident. Our findings provide a platform to support further evaluation of NPs for the discovery of new chemotypes that inhibit disease relevant CA enzymes.Full Tex

Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosis

Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment

Persistent systemic microbial translocation, inflammation, and intestinal damage during Clostridioides difficile infection

Background. Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods. Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results. Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P &lt; .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions. CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated

Ascaris lumbricoides &#946; carbonic anhydrase: A potential target enzyme for treatment of ascariasis

BACKGROUND: A parasitic roundworm, Ascaris lumbricoides, is the causative agent of ascariasis, with approximately 760 million cases around the world. Helminthic infections occur with a high prevalence mostly in tropical and developing xcountries. Therefore, design of affordable broad-spectrum anti-helminthic agents against a variety of pathogens, including not only A. lumbricoides but also hookworms and whipworms, is desirable. Beta carbonic anhydrases (β-CAs) are considered promising targets of novel anthelminthics because these enzymes are present in various parasites, while completely absent in vertebrates. METHODS: In this study, we identified an A. lumbricoides β-CA (AIBCA) protein from protein sequence data using bioinformatics tools. We used computational biology resources and methods (including InterPro, CATH/Gene3D, KEGG, and METACYC) to analyze AlBCA and define potential roles of this enzyme in biological pathways. The AlBCA gene was cloned into pFastBac1, and recombinant AIBCA was produced in sf-9 insect cells. Kinetics of AlBCA were analyzed by a stopped-flow method. RESULTS: Multiple sequence alignment revealed that AIBCA contains the two sequence motifs, CXDXR and HXXC, typical for β-CAs. Recombinant AIBCA showed significant CA catalytic activity with k(cat) of 6.0 × 10(5) s(−1) and k(cat)/K(M) of 4.3 × 10(7) M(−1) s(−1). The classical CA inhibitor, acetazolamide, showed an inhibition constant of 84.1 nM. Computational modeling suggests that the molecular architecture of AIBCA is highly similar to several other known β-CA structures. Functional predictions suggest that AIBCA might play a role in bicarbonate-mediated metabolic pathways, such as gluconeogenesis and removal of metabolically produced cyanate. CONCLUSIONS: These results open new avenues to further investigate the precise functions of β-CAs in parasites and suggest that novel β-CA specific inhibitors should be developed and tested against helminthic diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1098-5) contains supplementary material, which is available to authorized users

On the optimal contact potential of proteins

We analytically derive the lower bound of the total conformational energy of a protein structure by assuming that the total conformational energy is well approximated by the sum of sequence-dependent pairwise contact energies. The condition for the native structure achieving the lower bound leads to the contact energy matrix that is a scalar multiple of the native contact matrix, i.e., the so-called Go potential. We also derive spectral relations between contact matrix and energy matrix, and approximations related to one-dimensional protein structures. Implications for protein structure prediction are discussed.Comment: 5 pages, text onl