Can we disentangle predator-prey interactions from species distributions at a macro-scale? A case study with a raptor species.

There is a debate on whether an influence of biotic interactions on species distributions can be reflected at macro-scale levels. Whereas the influence of biotic interactions on spatial arrangements is beginning to be studied at local scales, similar studies at macro-scale levels are scarce. There is no example disentangling, from other similarities with related species, the influence of predator-prey interactions on species distributions at macro-scale levels. In this study we aimed to disentangle predator-prey interactions from species distribution data following an experimental approach including a factorial design. As a case of study we selected the short-toed eagle because of its known specialization on certain prey reptiles. We used presence-absence data at a 100 Km2 spatial resolution to extract the explanatory capacity of different environmental predictors (five abiotic and two biotic predictors) on the short-toed eagle species distribution in Peninsular Spain. Abiotic predictors were relevant climatic and topographic variables, and relevant biotic predictors were prey richness and forest density. In addition to the short-toed eagle, we also obtained the predictor's explanatory capacities for i) species of the same family Accipitridae (as a reference), ii) for other birds of different families (as controls) and iii) species with randomly selected presences (as null models). We run 650 models to test for similarities of the short-toed eagle, controls and null models with reference species, assessed by regressions of explanatory capacities. We found higher similarities between the short-toed eagle and other species of the family Accipitridae than for the other two groups. Once corrected by the family effect, our analyses revealed a signal of predator-prey interaction embedded in species distribution data. This result was corroborated with additional analyses testing for differences in the concordance between the distributions of different bird categories and the distributions of either prey or non-prey species of the short-toed eagle. Our analyses were useful to disentangle a signal of predator-prey interactions from species distribution data at a macro-scale. This study highlights the importance of disentangling specific features from the variation shared with a given taxonomic level.

Association between mannose-binding lectin deficiency and cytornegalovirus infection course after organ transplantation.

Background: Mannose binding lectin (MBL) is an innate humoral immune effector and MBL defi ciency has been suggested as a risk factor for the development of certain viral infections. However, there is no data about the possible association between MBL defi ciency and CMV, especially after organ transplantation. Methods: We measured MBL levels in 16 kidney transplant recipients with highrisk CMV serostatus (D+/R-) who received valganciclovir prophylaxis for 3 months (Study 1). In addition, MBL levels were retrospectively assayed in 55 recipients from a previous study of organ transplant recipients managed preemptively (Study 2). In Study 2, protracted CMV infection was associated with recipient CMV seronegativity, increasing age, and high viral load during the initial episode. In both studies, MBL defi ciency was diagnosed if MBL levels were <500 ng/ml. Results: In Study 1, after a follow-up of 12 months, 7 out of 16 patients developed CMV disease, 4 patients developed asymptomatic CMV infection, and 5 patients never developed any sign of CMV replication. Overall, 9/16 patients (56%) had MBL defi ciency: 5/7 (71%) of patients with CMV disease, 4/4 (100%) of patients with asymptomatic CMV infection, and 0/5 (0%) of patients without CMV infection (p=0.005, between CMV infection/disease versus no infection). Median MBL concentrations were higher in patients without CMV infection than in those with CMV infection (p<0.005). In Study 2, among 30 patients with CMV infection, 9/25 (36%) patients without MBL defi ciency had a protracted course, while 4/5 (80%) with MBL defi ciency did so (p=0.07). Conclusion: Data from two separate patient populations suggest that MBL defi ciency may be a signifi cant risk factor for late CMV disease/infection after prophylaxis, and protracted infection after preemptive treatment. This suggests a role for MBL in the control of CMV infection after organ transplantation.

Herpesvirus-associated B-cell proliferations

This article reviews the spectrum of Epstein-Barr virus and Kaposi sarcoma herpesvirus (KSHV/HHV-8)-associated B-cell lymphoid proliferations, their pathologic features and clinical presentation, diagnostic criteria, and pathogenetic aspects. Emphasis is on the differential diagnosis issues and difficulties that the pathologist may face for the correct identification and interpretation of these lesions.

Bridging basic science and clinical research - The EASL Monothematic Conference on Translational Research in Viral Hepatitis.

The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the conference held in Lyon, France on November 29-30, 2013. In recent years, great advances have been made in the field of viral hepatitis, particularly in hepatitis C virus (HCV) infection. The identification of IL28B genetic polymorphisms as a major determinant for spontaneous and treatment-induced HCV clearance was a seminal discovery. Currently, hepatologists are at the doorstep of even greater advances, with the advent of a wealth of directly acting antivirals (DAAs) against HCV. Indeed, promising results have accumulated over the last months and few years, showing sustained virological response (SVR) rates of up to 100% with interferon-free DAA combination therapies. Thus, less than 25years after its identification, HCV infection may soon be curable in the vast majority of patients, highlighting the great success of HCV research over the last decades. However, viral hepatitis and its clinical complications such as liver cirrhosis and hepatocellular carcinoma (HCC) remain major global challenges. New therapeutic strategies to tackle hepatitis B virus (HBV) and hepatitis D virus (HDV) infection are needed, as current therapies have undeniable limitations. Nucleoside/nucleotide analogues (NUC) can efficiently control HBV replication and reduce or even reverse liver damage. However, these drugs have to be given for indefinite periods in most patients to maintain virological and biochemical responses. Although sustained responses off treatment can be achieved by treatment with (pegylated) interferon-α, only about 10-30% of patients effectively resolve chronic hepatitis B. It was the goal of this conference to review the progress made over the last years in chronic viral hepatitis research and to identify key questions that need to be addressed in order to close the gap between basic and clinical research and to develop novel preventive and treatment approaches for this most common cause of liver cirrhosis and HCC.

Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome).

Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in differentiating keratinocytes and Langerhans cells in the epidermis. Our objective was to identify immunoreactive CLDN1 in human epidermal Langerhans cells and to examine the pattern of epidermal Langerhans cells in genetic human CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome]. Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies were analysed by confocal laser immunofluorescence microscopy and flow cytometry. Skin biopsy sections of two patients with NISCH syndrome were stained with an antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans cells and a subpopulation of keratinocytes from healthy skin were positive for CLDN1. The gross number and distribution of epidermal Langerhans cells of two patients with molecularly confirmed NISCH syndrome, however, was not grossly altered. Therefore, CLDN1 is unlikely to play a critical role in migration of Langerhans cells (or their precursors) to the epidermis or their positioning within the epidermis. Our findings do not exclude a role of this TJ molecule once Langerhans cells have left the epidermis for draining lymph nodes.

Poesia epica e letteratura femminile nell'Italia del XVII secolo: "L'Enrico, ovvero Bisanzio acquistato" (1635) di Lucrezia Marinelli

Nella mia tesi di dottorato mi concentro sul poema di Lucrezia Marinelli, L'Enrico, ovvero Bisanzio acquistato, pubblicato a Venezia nel 1635, indagando le strategie messe in atto dall'autrice per rivisitare il genere epico in un'ottica di riscatto femminile. Rispetto al canone epico e, in particolare, al modello di riferimento - la Gerusalemme liberata del Tasso - le vicende nodali sono, infatti, riscritte da un punto di vista chiaramente femminile. Pur occupandomi principalmente dell'opera di Marinelli, in alcuni casi nel corso del mio lavoro propongo dei confronti con altri poemi epici e cavallereschi prodotti da donne - in particolare I tredici canti del Floridoro di Moderata Fonte (1581) - volti a mostrare come le scrittrici avessero degli intenti comuni, dialogando in maniera critica con i modelli maschili da cui, tuttavia, traggono ispirazione. Nei primi capitoli del mio lavoro prendo in esame alcuni personaggi tradizionali dell'epica (le guerriere, la maga, ...) presenti ne L'Enrico e ne ripercorro gli episodi topici (le sortite notturne, l'eroe sull'isola, ...) dimostrando come, pur inserendosi coerentemente nel genere epico, siano caratterizzati in modo sostanzialmente diverso rispetto alla precedente tradizione maschile. Il primo capitolo si concentra sulle figure di guerriere, le quali presentano - rispetto ai precedenti modelli - differenze notevoli: non si lasciano coinvolgere in vicende amorose e non finiscono per essere sottomesse o uccise da un uomo, mantenendo così coerentemente intatti i valori di forza e indipendenza. Neppure la maga sull'isola - presa in esame nel capitolo dedicato alle Altre figure di donne idealizzate - è coinvolta in vicende sentimentali o caratterizzata sensualmente. L'autrice la rappresenta, non alla stregua di una tentatrice al servizio delle forze del male, ma come una donna colta, casta e disposta ad aiutare il cavaliere naufragato sulla sua isola. Nello stesso capitolo sono indagate anche altre figure femminili idealizzate, per taluni aspetti meno innovative, ma ugualmente interessanti: la Vergine, la personificazione di Venezia e la Musa. Queste rappresentazioni dal carattere iconico, presentano, infatti, diverse caratteristiche in comune con i personaggi più attivi del poema, le guerriere e la maga. Il capitolo Delle pene e delle tragedie amorose è dedicato all'amore e ai suoi esiti tragici. Le figure di donna coinvolte sono le madri, le mogli e Idillia, in cui è riconoscibile il personaggio topico della "damigella in difficoltà". Queste protagoniste, destinate a soffrire perché abbandonate dall'uomo che amano - il quale sente più forte il richiamo della guerra rispetto a quello dell'amore - servono da exempla, dimostrando che attaccamento affettivo e dipendenza conducono inesorabilmente all'infelicità. Rispetto al canone epico Marinelli riscatta alcune figure femminili, permettendo alle sue guerriere di prendersi la rivincita, vendicando la morte di eroine quali Camilla e Clorinda. Conseguentemente, alcuni guerrieri sono destinati a morire per mano di una donna. Nel quarto capitolo, mi concentro proprio su La sconfitta degli eroi, mettendo in luce come l'autrice proponga una sua personale regola del contrappasso, volta a cambiare (e addirittura invertire) le sorti dei personaggi che animano il suo poema. Questi aspetti risultano essere ancora più significativi se confrontati con l'opera - data alle stampe per la prima volta nel 1600 - intitolata Nobiltà et eccellenza delle donne. In questo trattato Marinelli sosteneva la superiorità del genere femminile su quello maschile. Alcune delle posizioni assunte nello scritto giovanile sono confermate dai personaggi e dalle vicende che animano l'Enrico. Confronti puntuali fra trattato e poema epico sono effettuati nell'ultimo capitolo del mio lavoro, sottolineando come fra le due opere vi siano delle affinità volte a confermare l'eccellenza delle donne.

The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the 'fused genes' family.

  The skin is essential for survival and protects our body against biological attacks, physical stress, chemical injury, water loss, ultraviolet radiation and immunological impairment. The epidermal barrier constitutes the primordial frontline of this defense established during terminal differentiation. During this complex process proliferating basal keratinocytes become suprabasally mitotically inactive and move through four epidermal layers (basal, spinous, granular and layer, stratum corneum) constantly adapting to the needs of the respective cell layer. As a result, squamous keratinocytes contain polymerized keratin intermediate filament bundles and a water-retaining matrix surrounded by the cross-linked cornified cell envelope (CE) with ceramide lipids attached on the outer surface. These cells are concomitantly insulated by intercellular lipid lamellae and hold together by corneodesmosmes. Many proteins essential for epidermal differentiation are encoded by genes clustered on chromosomal human region 1q21. These genes constitute the 'epidermal differentiation complex' (EDC), which is divided on the basis of common gene and protein structures, in three gene families: (i) CE precursors, (ii) S100A and (iii) S100 fused genes. EDC protein expression is regulated in a gene and tissue-specific manner by a pool of transcription factors. Among them, Klf4, Grhl3 and Arnt are essential, and their deletion in mice is lethal. The importance of the EDC is further reflected by human diseases: FLG mutations are the strongest risk factor for atopic dermatitis (AD) and for AD-associated asthma, and faulty CE formation caused by TG1 deficiency causes life-threatening lamellar ichthyosis. Here, we review the EDC genes and the progress in this field.

Prospective sampling based on model ensembles improves the detection of rare species

Identifying the geographic distribution of populations is a basic, yet crucial step in many fundamental and applied ecological projects, as it provides key information on which many subsequent analyses depend. However, this task is often costly and time consuming, especially where rare species are concerned and where most sampling designs generally prove inefficient. At the same time, rare species are those for which distribution data are most needed for their conservation to be effective. To enhance fieldwork sampling, model-based sampling (MBS) uses predictions from species distribution models: when looking for the species in areas of high habitat suitability, chances should be higher to find them. We thoroughly tested the efficiency of MBS by conducting an important survey in the Swiss Alps, assessing the detection rate of three rare and five common plant species. For each species, habitat suitability maps were produced following an ensemble modeling framework combining two spatial resolutions and two modeling techniques. We tested the efficiency of MBS and the accuracy of our models by sampling 240 sites in the field (30 sitesx8 species). Across all species, the MBS approach proved to be effective. In particular, the MBS design strictly led to the discovery of six sites of presence of one rare plant, increasing chances to find this species from 0 to 50%. For common species, MBS doubled the new population discovery rates as compared to random sampling. Habitat suitability maps coming from the combination of four individual modeling methods predicted well the species' distribution and more accurately than the individual models. As a conclusion, using MBS for fieldwork could efficiently help in increasing our knowledge of rare species distribution. More generally, we recommend using habitat suitability models to support conservation plans.

Adapter and enzymatic functions of proteases in T-cell activation.

Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T-cell receptor controls T-cell proliferation through proteases such as mucosa-associated lymphoid tissue 1 (MALT1) and Caspase-8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T-cell response and represent interesting targets of therapeutic immunomodulation.

LIGHT/HVEM/LTβR interaction as a target for the modulation of the allogeneic immune response in transplantation.

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTβR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance.

EASL Clinical Practice Guidelines: Wilson's disease.

This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers in the diagnosis and management of patients with Wilson's disease. The goal is to describe a number of generally accepted approaches for diagnosis, prevention, and treatment of Wilson's disease. Recommendations are based on a systematic literature review in the Medline (PubMed version), Embase (Dialog version), and the Cochrane Library databases using entries from 1966 to 2011. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system used in other EASL CPGs was used and set against the somewhat different grading system used in the AASLD guidelines (Table 1A and B). Unfortunately, there is not a single randomized controlled trial conducted in Wilson's disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines. The evaluation is mostly based on large case series which have been reported within the last decades.

What influence do anticoagulants have on oral implant therapy? A systematic review.

OBJECTIVES: This systematic review aims to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy (OAT) patient undergoing implant therapy and to provide a management protocol to patients under OAT undergoing implant therapy. MATERIAL AND METHODS: Medline, Cochrane Data Base of Systematic Reviews, the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. This search was completed by a hand research accessing the references cited in all identified publications. RESULTS: Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on OAT following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The OAT management strategies as well as the protocols during and after surgery were different. This heterogeneity prevented any possible data aggregation and synthesis. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the OAT patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These post-operative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes's application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies was a thromboembolic event reported. CONCLUSIONS: OAT patients (INR 2-4) who do not discontinue the AC medication do not have a significantly higher risk of post-operative bleeding than non-OAT patients and they also do not have a higher risk of post-operative bleeding than OAT patients who discontinue the medication. In patients with OAT (INR 2-4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. OAT discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on OAT is contraindicated.

Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients.

We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox regression models. One thousand two hundred thirty-nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R- vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14-9.14], pâeuro0/00<âeuro0/000.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63-2.17], pâeuro0/00=âeuro0/000.63). CMV disease was not associated with a lower graft failure-free survival (HR 1.27 [95% CI 0.64-2.53], pâeuro0/00=âeuro0/000.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63 [95% CI 1.01-2.64], pâeuro0/00=âeuro0/000.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.

Contribution of fine particulate matter sources to indoor exposure in bars, restaurants, and cafes

This study investigated the contribution of sources and establishment characteristics, on the exposure to fine particulate matter (PM(2.5)) in the non-smoking sections of bars, cafes, and restaurants in central Zurich. PM(2.5)-exposure was determined with a nephelometer. A random sample of hospitality establishments was investigated on all weekdays, from morning until midnight. Each visit lasted 30 min. Numbers of smokers and other sources, such as candles and cooking processes, were recorded, as were seats, open windows, and open doors. Ambient air pollution data were obtained from public authorities. Data were analysed using robust MM regression. Over 14 warm, sunny days, 102 establishments were measured. Average establishment PM(2.5) concentrations were 64.7 microg/m(3) (s.d. = 73.2 microg/m(3), 30-min maximum 452.2 microg/m(3)). PM(2.5) was significantly associated with the number of smokers, percentage of seats occupied by smokers, and outdoor PM. Each smoker increased PM(2.5) on average by 15 microg/m(3). No associations were found with other sources, open doors or open windows. Bars had more smoking guests and showed significantly higher concentrations than restaurants and cafes. Smokers were the most important PM(2.5)-source in hospitality establishments, while outdoor PM defined the baseline. Concentrations are expected to be even higher during colder, unpleasant times of the year. PRACTICAL IMPLICATIONS: Smokers and ambient air pollution are the most important sources of fine airborne particulate matter (PM(2.5)) in the non-smoking sections of bars, restaurants, and cafes. Other sources do not significantly contribute to PM(2.5)-levels, while opening doors and windows is not an efficient means of removing pollutants. First, this demonstrates the impact that even a few smokers can have in affecting particle levels. Second, it implies that creating non-smoking sections, and using natural ventilation, is not sufficient to bring PM(2.5) to levels that imply no harm for employees and non-smoking clients. [Authors]

Assessing the epidemiology and pattern of care of colorectal cancer in Valais, Switzerland

Background: The Valais's cancer registry (RVsT) of the Observatoire valaisan de le santé (OVS) and the department of oncology of Valais's Hospital conducted a study on the epidemiology and pattern of care of colorectal cancer in Valais. Colorectal cancer is the third cause of death by cancer in Switzerland with about 1600 deaths per year. It is the third most frequent cancer for males and the second most frequent for females in Valais. The number of new colorectal cancer cases (average per year) increased between 1989 and 2009 for males as well as for females in Valais. The number of colorectal cancer death cases (average per year) slightly increased between 1989 and 2009 for males as well as for females in Valais. Age-standardized rates of incidence were stable for males and females in Valais and in Switzerland between 1989 and 2009, while age-standardized rates of mortality decreased for males and females in Valais and Switzerland. Results: 774 cases were recorded (59% males). Median age at diagnosis was 70 years old. Most of cancers were invasive (79%) and the main localization was the colon (71%). The most frequent mode of detection was a consultation for non emergency symptoms (75%), but almost 10% of patients consulted in emergency. 82% of patients were treated within 30 days from diagnosis. 90% of the patients were treated by surgery alone or with combined treatment. The first treatment was surgery, including endoscopic resection in 86% of the cases. The treatment was different according to the localization and the stage of the cancer. Survival rate was 95% at 30 days and 79% at one year. The survival was dependent on the stage and the age at diagnosis. Cox model shows an association between mortality and age (better survival for young people) and between mortality and stage (better survival for the lower stages). Methods: RVsT collects information on all cancer cases since 1989 for people registered in the communes of Valais. RVsT has an authorization to collect non anonymized data. All new incident cancers are coded according to the International Classification of Diseases for Oncology (ICD-O-3) and the stages are coded according to the TNM classification. We studied all cases of in situ and invasive colorectal cancers diagnosed between 2006 and 2009 and registered routinely at the RVsT. We checked for data completeness and if necessary sent questionnaires to avoid missing data. A distance of 15 cm has been chosen to delimitate the colon (sigmoid) and the rectal cancers. We made an active follow-up for vital status to have a valid survival analysis. We analyzed the characteristics of the tumors according to age, sex, localization and stage with stata 9 software. Kaplan-Meier curves were generated and Cox model were fitted to analyze survival. Conclusion: The characteristics of patients and tumors and the one year survival were similar to those observed in Switzerland and some European countries. Patterns of care were close to those recommended in guidelines. Routine data recorded in a cancer registry can be used, not only to provide general statistics, but also to help clinicians assess local practices.