The Culicoides of the subgenus Avaritia (Diptera: Ceratopogonidae) in the Palaearctic region: through unsuspected diversity with epidemiologic implications

The biting midges of the genus Culicoides (Diptera: Ceratopogonidae) are known vectors of pathogens especially Orbivirus of the Reoviridae family such as bluetongue, african horse sickness, epizootic hemorrhagic disease and more recently Schmallenberg viruses. The western Europe and the Mediterranean basin faced bluetongue transmission with the 6 species belonging to the Avaritia subgenus recorded in these areas including the species closely related to the Obsoletus group. To date, no study encompasses the whole number of species belonging to a subgenus at a biogeographical scale. The data presented focus on local or on country fauna scale using a classification based on subgenus and/or group of species. Among the latter, the presence of cryptic species has been pointed out by recent phylogenetic studies. These classification discrepancies between authors since decades result in a taxonomic imbroglio. Recent findings of specimens with tricky morphology related to the Obsoletus group in France led us to better describe the systematic and the taxonomy of the subgenus Avaritia in the Palaearctic region. This study focuses on investigating the phylogenetic relationships between and within the Avaritia species of the Palaeactic region with a special interest for the Obsoletus group at a world scale. Voucher specimens were selected based on morphology, sequenced for the CO1 region (mtDNA) and then slide-mounted allowing a morphological interpretation of the results afterwards. A total of 82 CO1 sequences including 43 sequences from the GenBank database were analyzed by Bayesian inference and the resulting tree was used to study species boundaries. The Barcoding gap was evaluated for the closest related species not supported by the species delimitation analysis. Within the Avaritia subgenus, we propose a new systematic scheme for the species of the Obsoletus group including C. scoticus as a basal clade with the two following complexes: the Sanguisuga complex with the species C. abchazicus, C. gornostaevae, C. sanguisuga and C. sinanoensis; the Obsoletus complex made of the species C. obsoletus, C. montanus and a new species. Culicoides filicinus, absent in this analysis, could not be placed in the proposed scheme. The existence of Dewulfi and Chiopterus complex is discussed. The results of the species boundaries analysis and the presence of discriminant morphological characters support the evidence of two new species under description with one in the Obsoletus complex. We also point out new records of C. gornostaevae (France, Sweden and Switzerland) and C. aff. sanguisuga (Sweden). The subgenus Avaritia includes worldwide major vectors of Orbivirus. The revealed diversity increases up to 10 species in western Europe and questions about the possible vector roles in Europe of these newly recorded species. Evaluating the vector role of the Avaritia species in bluetongue and other viruses transmission reaches a higher challenging level for the European teams. (Texte intégral

What is new about the Culicoides identification freeware?

In the framework of Medreonet workpackage on "Regional surveillance of vectors", a Culicoides identification key based on morphology is proposed. This key will help to identify the different Culicoides species, including those of the Palaearctic region. The tool will be available in a freeware version and in a web version. At time of writing, the key was not yet available but a first draft version was to be presented soon after to Culicoides taxonomists so as to improve it. Currently, females of 85 species including 9 morphological variations are included in a database of 63 descriptors codified in 172 states. These descriptors and states of descriptors were discussed and validated by the participants of the last taxonomic meeting in Strasbourg, France, in March 2009. (Texte intégral

Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme (GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1–9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL+/PRLRHIGH GBM performed worse than PRL+/PRLRLOW GBM. In contrast, all male PRL+/PRLRHIGH GII-III patients were alive whereas only 30% of PRL+/PRLRLOW GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.Fil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: González, Nazareno. Laboratorio Max Planck de Biología Estructural, Química y Biofísica Molecular de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zuccato, Camila Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Abt, Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Orrillo, Santiago Jordi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Yael, Lastra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Fisiología Animal; ArgentinaFil: de Simone, Emilio Adrian. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Fisiología Animal; ArgentinaFil: Boutillon, Florence. Inserm; FranciaFil: Goffin, Vincent. Inserm; FranciaFil: Seilicovich, Adriana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Pisera, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ferraris, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin

On the orthogonal distance to class subspaces for high-dimensional data classification

The orthogonal distance from an instance to the subspace of a class is a key metric for pattern classification by the class subspace-based methods. There is a close relationship between the orthogonal distance and the residual standard deviation of a test instance from the class subspace. In this paper, we shall show that an established and widely-used relationship, between the residual standard deviation and the sum of squares of the residual PC scores, is not precise, and thus can lead to incorrect results, for the inference of high-dimensional data which nowadays are common in practice

Acetylcholine-treated murine dendritic cells promote inflammatory lung injury

In recent years a non-neuronal cholinergic system has been described in immune cells, which is often usually activated during the course of inflammatory processes. To date, it is known that Acetylcholine (ACh), a neurotransmitter extensively expressed in the airways, not only induces bronchoconstriction, but also promotes a set of changes usually associated with the induction of allergic/Th2 responses. We have previously demonstrated that ACh polarizes human dendritic cells (DC) toward a Th2-promoting profile through the activation of muscarinic acetylcholine receptors (mAChR). Here, we showed that ACh promotes the acquisition of an inflammatory profile by murine DC, with the increased MHC II IAd expression and production of two cytokines strongly associated with inflammatory infiltrate and tissue damage, namely TNF-α and MCP-1, which was prevented by blocking mAChR. Moreover, we showed that ACh induces the up-regulation of M3 mAChR expression and the blocking of this receptor with tiotropium bromide prevents the increase of MHC II IAd expression and TNF-α production induced by ACh on DC, suggesting that M3 is the main receptor involved in ACh-induced activation of DC. Then, using a short-term experimental murine model of ovalbumin-induced lung inflammation, we revealed that the intranasal administration of ACh-treated DC, at early stages of the inflammatory response, might be able to exacerbate the recruitment of inflammatory mononuclear cells, promoting profound structural changes in the lung parenchyma characteristic of chronic inflammation and evidenced by elevated systemic levels of inflammatory marker, TNF-α. These results suggest a potential role for ACh in the modulation of immune mechanisms underlying pulmonary inflammatory processes.Fil: Gori, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Alcain, Julieta María. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Vanzulli, Silvia. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Moreno Ayala, Mariela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Jancic, Carolina Cristina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; ArgentinaFil: Vermeulen, Elba Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; ArgentinaFil: Salamone, Gabriela Veronica. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

The Advanced Air Mobility: an overview of the drone industry and its application in the healthcare sector

LAUREA MAGISTRALENegli ultimi anni, l’utilizzo degli UAV in ambito sanitario ha attirato l’attenzione di numerosi stakeholders del mondo accademico e di quello industriale. Diversi studi hanno analizzato come questa tecnologia innovativa possa essere incorporata in contesti medici e hanno evidenziato una relazione positiva tra l’uso dei droni e l’efficienza operativa. L'industria globale dei droni per il settore sanitario rappresenta un ambito tanto interessante quanto ancora poco applicato. Sebbene la tecnologia dei droni risalga a molti decenni fa, negli ultimi anni ha fatto passi da gigante, in particolare nelle applicazioni in campo medico. Tuttavia, nonostante la vasta letteratura sulle tecnologie innovative, esistono pochi studi specifici che abbiano esaminato in profondità l'adozione dei droni nel settore sanitario. Pertanto, lo scopo di questa tesi, sviluppata in collaborazione con l’Osservatorio Droni e Mobilità Aerea Avanzata del Politecnico di Milano, è quello di realizzare un censimento globale delle applicazioni dei droni nel settore sanitario, studiare le caratteristiche di questa industria emergente, comprendere come queste soluzioni tecnologiche vengano adottate nelle strutture sanitarie e, infine, analizzare le variabili che influenzano tale adozione.In recent years, the use of UAVs in healthcare has captured the attention of numerous academic and industrial stakeholders. Several studies have analyzed how this innovative technology can be integrated into medical contexts and have highlighted a positive relationship between drone usage and operational efficiency. The global drone industry for the healthcare sector represents an area that is both fascinating and still underutilized. Although drone technology dates back many decades, it has made significant strides in recent years, particularly in medical applications. However, despite the extensive literature on innovative technologies, there are few specific studies that have thoroughly examined the adoption of drones in the healthcare sector. Therefore, the purpose of this thesis, developed in collaboration with the Drones and Advanced Air Mobility Observatory of the Politecnico di Milano, is to conduct a global census of drone applications in healthcare, study the characteristics of this emerging industry, understand how these technological solutions are being adopted in healthcare facilities, and finally, analyze the variables that influence this adoption

Role of CDK9 in skeletal muscle

Cdk9 is a member of cyclin-dependent kinases and it is expressed in human and murine tissue with high levels in terminally differentiated cells. The elevated levels of Cdk9 and its regulatory subunits in terminally differentiated cells, together with the fact that it is implicated in the regulation of transcriptional elongation via phosphorylation of CTD of RNA polII, distinguishes Cdk9 from the other cdks. Cyclin partners of CDK9 are cyclin T1, T2a, T2b and K, with a formation of a complex, called p-TEF-B. In Hela cells about 80% of cellular P-TEFb is composed of cyclin T1 and the cyclin –dependent kinase 9 (CDK9), and about 20% of cellular CDK9 is complexed to other cyclins, such as cyclin T2a, T2b and with cyclin K. It was demonstrated that CdK9 complexed with CyT2a plays a role in the activation of myogenic program and Cdk9-CyT2a activity is not down-regulated in myotube formation, but its activation contributes to the transcriptional activity MyoD-mediated during myogenic program. The formation of a multimeric complex, containing cdk9/cyclin T2a and MyoD is present in muscle cells during the activation of the differentiation program and the N-terminal region of Cdk9 directly interacts with the b-HLH region of MyoD, allowing the formation of a complex also containing cyclin T2a. Recently a 55 kDa protein called CDK9-55 has been identified. This isoform presents 117 additional amminoacids residues at the N-terminal portion of Cdk9-42 and it conserves all molecular features of 42 isoform, indeed it associates with CycT phosphorylates CTD of RNA polII. Cdk9-55 is significantly upregulated in cells induced to differentiate, either in C2C12 cells or in satellite isolated cells, and it was demonstrated that there is a clear induction of cdk9-55 expression in injured skeletal muscles. Analysis in vivo on limbs at different times of development demostrated a different correlation between two CDK9 isoforms: CDK9-55 is involved during foetal myogenesis, whereas the CDK9-42 is expressed during embrional myogenesis. Study in vitro demonstrated that CDK9-55 is the isoform more expressed during differentiation both embrional and fetal myoblasts. A new antibody, p-CDK9, permitted us to define CDK9-55 as the active isoform during the differentiation. CDK9-55 is also the isoform more expressed during the re-innervation process. The analysis of different cyclins that complex with different members of kinase proteins showed that in vivo only cyclin K and D3 are involved during foetal myogenesis, suggesting their interaction with CDK9-55, whereas Cyclin T1, T2, L and H are implicated during primary myogenesis, in concomitance with CDK9-42 expression. Study in vitro demonstrated that only cyclin T2 is involved during the differentiation process for embrional and fetal myoblasts. Between inhibitory post transcriptional regulator mechanism of CDK9 there is the interaction with 7SKsnRNA and HEXIM1, our studies, on C2C12 cells, by RIP assay demonstrated that CDK9 isn’t associated with 7SKsnRNA/Hexim1 during differentiative phase, supporting that in differentiation CDK9 is active

Adenoviral vector-mediated gene therapy for gliomas: coming of age

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and it carries a dismal prognosis. Adenoviral vector (Ad)-mediated gene transfer is being developed as a promising therapeutic strategy for GBM. Preclinical studies have demonstrated safety and efficacy of adenovirus administration into the brain and tumor mass in rodents and into the non-human primates' brain. Importantly, Ads have been safely administered within the tumor resection cavity in humans. AREAS COVERED: This review gives background on GBM and Ads; we describe gene therapy strategies for GBM and discuss the value of combination approaches. Finally, we discuss the results of the human clinical trials for GBM that have used Ads. EXPERT OPINION: The transduction characteristics of Ads, and their safety profile, added to their capacity to achieve high levels of transgene expression have made them powerful vectors for the treatment of GBM. Recent gene therapy successes in the treatment of retinal diseases and systemic brain metabolic diseases encourage the development of gene therapy for malignant glioma. Exciting clinical trials are currently recruiting patients; although, it is the large randomized Phase III controlled clinical trials that will provide the final decision on the success of gene therapy for the treatment of GBM.Fil: Castro, María G.. University of Michigan; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Wilson, Thomas J.. University of Michigan; Estados UnidosFil: Calinescu, Alexandra. University of Michigan; Estados UnidosFil: Paran, Christopher. University of Michigan; Estados UnidosFil: Kamran, Neha. University of Michigan; Estados UnidosFil: Koschmann, Carl. University of Michigan; Estados UnidosFil: Moreno Ayala, Mariela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Assi, Hikmat. University Of Michigan Medical School;Fil: Lowenstein, Pedro R.. University of Michigan; Estados Unido

IIKC: An Interactive Identification Key for female Culicoides (Diptera: Ceratopogonidae) from the West Palearctic region

In 2006, bluetongue virus (BTV) outbreaks appeared surprisingly in northern Europe and widely affected most of the European countries. Correct identification of Culicoides species (Diptera: Ceratopogonidae), known as BTV vectors, is a key component of all studies intending to understand vector dynamics and to develop vector control strategies. A computer-based system, Xper2, was used to develop an Interactive Identification Key (IIKC) for female Culicoides from the West Palearctic region. The current version of IIKC includes 108 taxa, 61 descriptors and 837 pictures and schemes. IIKC is a powerful tool for routinely identifying Culicoides species and for training young specialized taxonomists

Cytokine Profiles in Toxoplasmic and Viral Uveitis

BackgroundUveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context MethodsUsing a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract ResultsFive mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-γ, IL-6, and macrophage inflammatory protein-1β were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis ConclusionsWe found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatmen