QUATERNARY BUILD-UPS AND RHODALGAL CARBONATES ALONG THE ADRIATIC AND IONIAN COASTS OF THE ITALIAN PENINSULA: A REVIEW

In the Mediterranean, build-ups (created by coralline algae, Cladocora caespitosa, deep-water corals, vermetids, polychaetes and bacteria) and rhodolith beds are important hot-spots of biodiversity. Being severely threatened by anthropogenic impact and climate change, they have been included in international directives on environmental protection. This work wants to support the ongoing research on modern bioconstructions by providing further data on the long-term effects of environmental factors on these habitats. Our results are based on the analysis of the existing literature on the outcropping Quaternary successions of the Adriatic and Ionian coasts of peninsular Italy. The existing reports of build-ups and rhodalgal carbonates have been summarized in an homogeneous data-set and then studied to highlight distribution patterns in space and time. The analyses consistently outlined the importance of sedimentation rate in controlling the general distribution of build-ups and rhodalgal carbonates. The majority of the reports is concentrated south of the Gargano, where the sediment-load of the rivers is small. The majority of the reports is related to coralline algae, suggesting that they were the main carbonate producers during the period. C. caespitosa general distribution is mainly controlled by temperature, with most of the occurrences dating back to the warm periods of the late Ionian and of the Tarantian. Large build-ups of Cladocora are restricted to embayments and gulfs well-protected against storm waves. The distribution of the outcrops of deep-water corals is biased by the geological setting. A remarkable uplift is necessary to bring these corals from their original deep-water setting to elevated areas onshore. Consequently, most of the outcrops are in Southern Calabria which is characterized by a strong Quaternary uplift. Chemosynthetic build-ups, intertidal bioconstructions (made by vermetids, polychaetes or coralline algae), as well as stromatolites, are rare in the study area

Microscale thermophoresis and docking studies suggest lapachol and auraptene are ligands of IDO1.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key target for the development of small molecule immunotherapies in oncology. In this framework, the screening of chemotherapeutic agents to identify compounds binding to IDO1 represents a valuable strategy for the development of multitarget drug candidates that combine synergic immunoregulatory properties to cytotoxic activity. In this study, we report that two natural compounds endowed with anticancer activity, namely lapachol and auraptene, act as IDO1 ligands with dissociation constant (Kd) in the micromolar range of potency. Docking studies provide plausible binding modes of these compounds to the catalytic cleft of IDO1. Our results support the notion that lapachol and auraptene may be considered interesting lead compounds in the immuno-oncology setting

LOWER OLIGOCENE CORALLINE ALGAE OF THE UROMIEH SECTION (QOM FORMATION, NW IRAN) AND THE OLDEST RECORD OF <em>TITANODERMA PUSTULATUM</em> (CORALLINOPHYCIDAE, RHODOPHYTA)

The Rupelian Uromieh section of the Qom Formation was analyzed with the aim to provide a first description of its coralline algal assemblages, and benthic paleoenvironmental evolution through time. The presence of Nummulites fichteli, Nummulites vascus, Halkyardia maxima and Subterraniphyllum thomasii, together with the absence of Nephrolepidina and Eulepidina confirm an early to middle Rupelian age. In the lower part of the section, the abundance of miliolids and corals suggests a proximal inner-platform environment, while upsection the increase in large rotaliids, coralline algae and bryozoans points toward a distal inner-platform/proximal middle-platform setting. Coralline algal assemblages support this interpretation, with Sporolithales and Hapalidiales becoming more common in the upper part of the section. Within the coralline assemblage, Lithoporella melobesioides and Titanoderma pustulatum are two of the most common species, together with articulated coralline algae. S. thomasii is more common in  coral-rich intervals, confirming that the distribution of this species was confined to shallow-water environments. The specimens of T. pustulatum recovered in the Uromieh section predate all the other known records of this species, indicating that the origin of T. pustulatum should be dated at least at the early Rupelia

Binding properties of different categories of IDO1 inhibitors: a microscale thermophoresis study

Aim: Inhibition of IDO1 is a strategy pursued in the immune-oncology pipeline for the development of novel anticancer therapies. At odds with an ever-increasing number of inhibitors being disclosed in the literature and patent applications, only very few compounds have hitherto advanced in clinical settings. Materials & methods: We have used MicroScale Thermophoresis analysis and docking calculations to assess on a quantitative basis the binding properties of distinct categories of inhibitors to IDO1. Results: Results shed further light on hidden molecular aspects governing the recognition by the enzyme of compounds with different mechanism of inhibition. Conclusion: Results pinpoint specific binding features of distinct inhibitors to IDO1 that offer clues for the design of next-generation inhibitors of the enzyme

Polysynovitis in a horse due to Borrelia burgdorferi sensu lato infection – Case study

Lyme borreliosis (LB) is a multi-systemic tick-borne disease affecting both humans and animals, including horses, and is caused by a group of interrelated spirochetes classified within the Borrelia burgdorferi sensu lato (s.l.) complex. Despite the high reported seroprevalence in the European equine population for B. burgdorferi s.l., to-date no documented clinical cases have been described. A 6-year-old Paint gelding was referred with a history of three weeks of fever, intermittent lameness and digital flexor tendon sheath effusion of the right hind limb. Based on a strict diagnostic protocol, which included serological tests for infectious diseases and molecular investigations, a final diagnosis was made of polysynovitis due to B. burgdorferi s.l. infection. An unreported aspect observed in this case was the absence of the pathogen DNA in two of the affected joints. To the authors' knowledge, the case described represents the first documented clinical case of equine LB in Italy. Moreover, the absence of pathogen DNA in two of the affected joints observed in this case revealed a possible similarity with the same condition described in humans, where an immunomediated pathogenesis for arthropathy due to B. burgdorferi s.l. infection is suspected. Since humans and horses share the same habitat, this report supports the role of the horse as potential sentinel for human biological risk

Fragment-based approach to identify IDO1 inhibitor building blocks

Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) is attracting a great deal of interest as drug target in immune-oncology being highly expressed in cancer cells and participating to the tumor immune-editing process. Although several classes of IDO1 inhibitors have been reported in literature and patent applications, only few compounds have proved optimal pharmacological profile in preclinical studies to be advanced in clinical trials. Accordingly, the quest for novel structural classes of IDO1 inhibitors is still open. In this paper, we report a fragment-based screening campaign that combines Water-LOGSY NMR experiments and microscale thermophoresis approach to identify fragments that may be helpful for the development of novel IDO1 inhibitors as therapeutic agents in immune-oncology disorders

Transmission through graphene of electrons in the 30 – 900 eV range

Here, we report on accurate transmission measurements of electrons below 1 keV through suspended monolayer graphene. Monolayer graphene was grown via chemical vapor deposition and transferred onto transmission electron microscopy (TEM) grids. A monochromatic electron gun has been employed to perform the measurements in the 30 – 900 eV range in ultra-high vacuum. The graphene transparency is obtained from the absolute measurement of the direct beam current and the transmitted one, by means of a Faraday cup. We observed a transmission going from 20 to 80% for monolayer graphene within the experimental electron energy range. The high quality and the grid coverage of the suspended graphene has been proved via micro-Raman, X-ray photoemission, electron energy loss spectroscopies and field-emission scanning electron microscopy. After a 550 °C in-vacuum annealing of the samples, the main contribution to the C 1s spectrum is due to the component and the evidence of suspended monolayer graphene has been observed through the -plasmon excitation

The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood

Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has invitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (13mg/m(2)/dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (81%) died due to infections. Twenty-seven patients (729%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 01%. Twenty-two of 30 BCP-ALL patients (733%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 313%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 684%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London