The function of MLO, a negative regulator of defence, is conserved in monocot and dicot plants

Host cell entry is a critical step during pathogenesis of many microbial pathogens including animal pathogenic bacteria and fungal parasites of plants. Some microbes exploit human chemokine G-protein coupled receptors (GPCRs) to enter host cells. Barley MLO, the prototype of a plant-specific protein family, exhibits a topology and subcellular localisation that is reminiscent of GPCRs. Mutations in barley MLO confer resistance against all known isolates of the powdery mildew fungus, Blumeria gramis f. sp. hordei (Bgh), suggesting that MLO function might be exploited for pathogenesis by the fungal parasite. The cytosolic calcium sensor calmodulin was previously identified as a protein interacting with MLO in vivo and was shown to enhance mlo-mediated susceptibility in planta. To identify further proteins that physically interact with A. thaliana MLO isoforms, the yeast split-ubiquitin system was employed. This revealed calmodulin as a common interactor of MLO proteins and identified four additional candidate interactors. To unravel their potential function in defence modulation, barley homologues of the selected candidate genes were tested by transient expression in single barley epidermal cells. However, neither dsRNAi-mediated gene silencing nor overexpression revealed a significant effect on Bgh penetration success in either wild-type (MLO) or mutant (mlo) genotypes. Recently, a gene required for mlo-mediated resistance (ROR2) in barley was found to encode a plasma membrane-resident syntaxin protein. In addition, a genetic screen to identify A. thaliana mutants enabling enhanced entry of the inappropriate Bgh fungus led to the identification of PEN1. The gene was shown to encode a syntaxin that is functionally homologous to barley ROR2. In this study, A. thaliana MLO proteins were demonstrated to interact with a subset of syntaxins in the yeast split-ubiquitin system. To date, it was unclear whether durable broad-spectrum mlo-mediated resistance is a feature restricted to the monocot barley. In this study, A. thaliana insertion mutants of the candidate ortholog of barley MLO, AtMLO2, were isolated and found to be resistant against the powdery mildew fungus Golovinomyces orontii. In addition, Atmlo2 mutants exhibit enhanced resistance to inappropriate powdery mildew fungi. In contrast, infection phenotypes to bacterial or oomycete pathogens appeared unaltered. These results indicate that MLO function is evolutionarily conserved in both monocot and dicot plant species. It is therefore possible that the ability of powdery mildew fungi to target specific MLO isoforms for entry into plant cells was invented at least 200 million years ago

Libraries at sixes and sevens: a few considerations on the book Library analytics and metrics, edited by Ben Showers

Although libraries can count on precious data sets covering users’ personal data and habits, not very many are profiting from the potential of analytics to make informed decisions and ultimately drive new services. Library analytics and metrics: using data to drive decisions and services delves into some of the key issues in the use of data analytics and metrics, accompanying each chapter by short, practical case studies. This review focuses on the legal and ethical risks, and possible ways to uncover new insights and exploiting their use with an Italian perspective. The vital need of networking and sharing data is also stressed.Oggi le biblioteche possono contare, più o meno consapevolmente, su una serie di dati preziosi relativi agli utenti e ai loro interessi. Tuttavia sono ancora troppo poche le istituzioni che utilizzano questi dati per migliorare i servizi offerti. Il libro Library analytics and metrics: using data to drive decisions and services cerca di fare il punto su questo tema, offrendo alla comunità bibliotecaria degli strumenti per riflettere sui numerosi aspetti legati alla raccolta dei dati e al loro utilizzo. In questa recensione vengono analizzati in particolare gli aspetti legali ed etici e le modalità di raccolta e utilizzo dei dati, facendo riferimento al contesto italiano. Viene inoltre sottolineata l’importanza di fare rete e di condividere i dati per creare un sistema nazionale e internazionale di valutazione

The evaluation of real-world digital libraries : a case at the Loughborough University Library

Evaluation is a crucial step for the development and improvements of digital libraries. Unfortunately, nowadays only few studies are focused on this matter and even fewer concentrate on how evaluation is conducted in real-world digital libraries. The study contributes to the research presenting the results of a qualitative case study conducted at the Loughborough University Library, based on data collected from eleven semi-structured interviews and document analysis. It reports how evaluation is conducted in a real-world digital library, which are the knowledge and competences of the staff in charge of performing it, which are the obstacles and barriers encountered by the staff and it examines what happens after the conclusion of the evaluation, in particular how results and recommendations are turned to profitable account. The research also aims to act as source of references for researchers who want to investigate this field further. The collected data were analyzed trough constant comparative process and seven main categories matching the research objectives were identified and discussed: definition of evaluation by the interviewees, conceptual purpose of evaluation according to the interviewees, training on evaluation by the interviewees, problems, time constrains, resources, cooperation within the group, individual attitude, project planning, project development, how implement actions from recommendations, dissemination of results, sections taken to implement the recommendations, impact of evaluation projects. Recommendations for the Loughborough University Library and indications for further investigations are also discussed. The research confirms that currently the knowledge about how real-world-digital libraries deals with evaluation are insufficient and it raises several new and controversial questions, which should force the scientific community to investigate deeper the reality of digital library.Joint Master Degree in Digital Library Learning (DILL

Cone-Beam Computed Tomographic Assessment of the Mandibular Condylar Volume in Different Skeletal Patterns: A Retrospective Study in Adult Patients

The aim of this study was to assess the condylar volume in adult patients with different skeletal classes and vertical patterns using cone‐beam computed tomography (CBCT). CBCT scans of 146 condyles from 73 patients (mean age 30   12 years old; 49 female, 24 male) were selected from the archive of the Department of Dentistry and Maxillofacial Surgery of Fondazione IRCCS Ca’ Granda, Milan, Italy, and retrospectively analyzed. The following inclusion criteria were used: adult patients; CBCT performed with the same protocol (0.4 mm slice thickness, 16   22 cm field of view, 20 s scan time); no systemic diseases; and no previous orthodontic treatments. Three‐dimensional cephalometric tracings were performed for each patient, the mandibular condyles were segmented and the relevant volumes calculated using Mimics Materialize 20.0  software (Materialise, Leuven, Belgium). Right and left variables were analyzed together using random‐intercept linear regression models. No significant association between condylar volumes and skeletal class was found. On the other hand, in relation to vertical patterns, the mean values of the mandibular condyle volumes in hyperdivergent subjects (688 mm3) with a post‐rotation growth pattern (625 mm3) were smaller than in hypodivergent patients (812 mm3) with a horizontal growth pattern (900 mm3). Patients with an increased divergence angle had smaller condylar volumes than subjects with normal or decreased mandibular plane divergence. This relationship may help the clinician when planning orthodontic treatment

Myeloid-Derived Suppressor Cells: Ductile Targets in Disease

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an “emergency state” that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease

The p50 NF-\u3baB subunit is a prognostic regulator of colorectal cancer-associated inflammation

In most tumors, tumor associated macrophages (TAMs) express an M2-skewed phenotype and are therefore associated with unfavorable prognosis. However, the impact of TAMs in colorectal cancer (CRC) development and outcome is still controversial. We first demonstrate, by parallel studies in colitis-associated cancer (CAC) and in genetically driven ApcMin mouse models, that p50 NF-\u3baB is essential for CRC development by restraining M1-dependent antitumor response. In absence of p50 mice developed fewer and smaller CRC lesions which express enhanced levels of M1/Th1 cytokines/chemokines including IL-12 and CXCL10, whose administration restrained CAC development in vivo. Moreover colons from p50-/- tumor bearers showed a reduced number of TAMs, as opposed to increased NK, NKT, CD8+ T cells and apoptotic cancer cells. Consistently, in CRC patients, high burden of p50+ TAMs was associated with decreased M1/Th1 inflammation and worse outcome indicating p50 as a new candidate for prognostic and target therapeutic intervention

The cognitive and behavioural profile of Amyotrophic Lateral Sclerosis: Application of the consensus criteria

Abstract. OBJECTIVE: The study aims to assess the spectrum of cognitive and behavioural disorders in patients affected by Amyotrophic Lateral Sclerosis (ALS) according to the recent consensus criteri

Immunometabolic interference between cancer and COVID-19

Even though cancer patients are generally considered more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the mechanisms driving their predisposition to severe forms of coronavirus disease 2019 (COVID-19) have not yet been deciphered. Since metabolic disorders are associated with homeostatic frailty, which increases the risk of infection and cancer, we asked whether we could identify immunometabolic pathways intersecting with cancer and SARS-CoV-2 infection. Thanks to a combined flow cytometry and multiomics approach, here we show that the immunometabolic traits of COVID-19 cancer patients encompass alterations in the frequency and activation status of circulating myeloid and lymphoid subsets, and that these changes are associated with i) depletion of tryptophan and its related neuromediator tryptamine, ii) accumulation of immunosuppressive tryptophan metabolites (i.e., kynurenines), and iii) low nicotinamide adenine dinucleotide (NAD+) availability. This metabolic imbalance is accompanied by altered expression of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs), with a distinctive downregulation of IL-6 and upregulation of IFNγ mRNA expression levels. Altogether, our findings indicate that cancer not only attenuates the inflammatory state in COVID-19 patients but also contributes to weakening their precarious metabolic state by interfering with NAD+-dependent immune homeostasis

Cognitive Syndromes and C9orf72 Mutation Are Not Related to Cerebellar Degeneration in Amyotrophic Lateral Sclerosis

ObjectiveThe notion that cerebellar pathology may contribute to cognitive impairment in ALS, especially in patients with C9orf72 repeated expansion, has been inconsistently reported. This study aimed exploring the relationship between cerebellar involvement, cognitive impairment and C9orf72 repeated expansion of patients with ALS.MethodsQuantitative in vivo assessment of cerebellar lobules has been investigated in 66 non-demented patients with ALS and 28 healthy controls (HCs). Pathologic C9orf72 repeated expansion was found in 13 patients. Mild cognitive and/or behavioral impairment was diagnosed in 22 C9orf72 negative ALS patients. Measures of cortical volume (CV) and cortical thickness (CT) of cerebellar lobules of all participants were used for Principal Component Analysis (PCA) to identify clusters of lobular measures highly correlated with each other. PCA outcomes were used for between group comparisons and correlation analyses with neuropsychological and clinical features.ResultsDisease severity measured with ALS functional rating scale and index of disease progression rate significantly correlated with CV reduction of the second PCA cluster loading CV measures of anterior lobules. In all patients, cognitive impairment, measured with verbal fluency, was related to CV reduction of the third cluster comprising posterior lobules. No specific cortical thinning or volume reduction of cerebellar clustering patterns could be detected in ALS subgroups.ConclusionOur data show that specific patterns of subregional cerebellar involvement are associated with physical disability or cognitive impairment in ALS, in line with the topographic organization of the cerebellum. However, there was no specific correlation between cerebellar degeneration and cognitive syndromes or C9orf72 mutations