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The microbiome and autoimmunity: a paradigm from the gut–liver axis

Cellular & Molecular Immunology 2018年第6期15卷 595-609页

作者： Bo Li carlo Selmi Ruqi Tang ME Gershwin Xiong Ma Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive DiseaseShanghai 200001China Division of Rheumatology and Clinical Immunology Humanitas Research HospitalRozzanoItaly BIOMETRA Department University of Milan MilanItaly Division of Rheumatology Department of MedicineAllergy and Clinical ImmunologyUniversity of California at DavisDavisCAUSA

Microbial cells significantly outnumber human cells in the body,and the microbial flora at mucosal sites are shaped by environmental factors and,less intuitively,act on host immune responses,as demonstrated by experimental data in germ-free and gnotobiotic *** understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown,as observed in rheumatic fever triggered by Streptococci via molecular mimicry,epitope spread and bystander *** availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases,including rheumatoid arthritis,type 1 diabetes,multiple sclerosis and autoimmune liver *** remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere *** fact,there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity,and microbial therapeutics is being investigated to prevent or halt autoimmune *** a putative mechanism,it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens,giving rise to the differentiation of autoreactive Th17 cells and other T helper *** comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity,with an emphasis on how dysbiosis may influence systemic *** particular,a gut–liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm,considering its anatomic and physiological connections.

关键词： autoimmunity autoimmune liver disease dysbiosis microbiome

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Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

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World Journal of Gastroenterology 2016年第38期22卷 8447-8458页

作者： Michele Merli Giuseppe Carli Luca Arcaini carlo Visco Division of Hematology University Hospital Ospedale di Circolo & Fondazione MacchiUniversity of Insubria Department of Cell Therapy and Hematology San Bortolo Hospital Department of Molecular Medicine University of Pavia

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

关键词： Non-hodgkin lymphomas Hepatitis C virus Antiviral therapy Interferon Ribavirin Sofosbuvir Direct-acting antiviral agents Marginal zone lymphomas

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Biomimetics of Campaniform Sensilla:Measuring Strain from the Deformation of Holes

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Journal of Bionic Engineering 2007年第2期4卷 63-76页

作者： Julian F. V. Vincent Sally E. Clift carlo Menon Department of Mechanical Engineering The University of BathBath BA2 7AYUK Advanced Concepts Team European Space Agency2201 AZ NoordwijkThe Netherlands

We present a bio-inspired strategy for designing embedded strain sensors in space structures. In insects, the campaniform sensillum is a hole extending through the cuticle arranged such that its shape changes in response to loads. The shape change is rotated through 90° by the suspension of a bell-shaped cap whose deflection is detected by a cell beneath the cuticle. It can be sensitive to displacements of the order of 1 nm. The essential morphology, a hole formed in a plate of fibrous composite mate- rial, was modelled by Skordos et al. who showed that global deformation of the plate （which can be flat, curved or a tube） induces higher local deformation of the hole due to its locally higher compliance. Further developments reported here show that this approach can be applied to groups of holes relative to their orientation. , The morphology of the sensillum in insects suggests that greater sensitivity can be achieved by arranging several holes in a regular pattern; that if the hole is oval it can be ＂aimed＂ to sense specific strain directions; and that either by controlling the shape of the hole or its relationship with other holes it can have a tuned response to dynamic strains. We investigate space applications in which novel bio-inspired strain sensors could successfully be used.

关键词： campaniform sensillum strain displacement compliance hole remote sensing fibrous composite

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Witness for resolution: post-conflict quadratic affiliation in semi-free ranging pigs

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Current Zoology 2024年第2期70卷 233-243页

作者： Ivan Norscia Edoardo Collarini carlo Robino Elena Chierto Giada Cordoni Department of Life Sciences and Systems Biology University of TorinoVia Accademia Albertina 1310123 TorinoItaly Department of Public Health Sciences and Pediatric s University of TorinoC.So Galileo Galilei 2210126 TorinoItaly

In social mammals,post-conflict resolution can involve the reunion of former opponents(reconciliation),spontaneous/solicited post-conflict affliation of a third party with either opponent(triadic contacts),and affiliation between other individuals(hereafter bystanders;quadratic contacts).Quadratic contacts-possibly informing complex cognitive abilities-have been neglected in post-conflict *** investi-gated quadratic affliation in semi-free ranging pigs Sus scrofa,at the ethical farm Parva-Domus(Cavagnolo,Italy).Kinship was *** collected behavioral data on adult pigs(n=104)via video recordings(43 h)followed by video *** and anxiety behaviors between bystanders were collected under post-conflict(PC;following a conflict between non-bystanders)and matched-control(MC;no conflict)*** affiliation was present in pigs,as bystanders affliated more in PC than MC,and such affiliation was followed by a decrease in the anxiety behaviors of both the interacting ***,quadratic contacts may be partly aimed at reducing one's own anxiety(intrinsic regulation).Quadratic affiliation was highest between closely related bystanders,which suggests that such affiliation may be most effective when close kin is *** affiliation was lowest after reconciliation and spontaneous triadic *** suggests that direct peacemaking between opponents and spontaneous triadic contacts with close kin may most likely replace quadratic ***,pigs can be influenced by the negative events that affect other pigs-but not themselves-and their response may be modulated by social *** non-random quadratic affiliation may point toward the presence of elements of social appraisal abilities inpigs.

关键词： anxiety reduction emotional regulation reconciliation social appraisal triadic contacts.

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Prospective evaluation of a new device for the treatment of anal fistulas

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World Journal of Gastroenterology 2016年第30期22卷 6936-6943页

作者： carlo Ratto Francesco Litta Lorenza Donisi Angelo Parello proctology unit Department of Surgical Sciences Catholic University 00168 Rome Italy

AIM: To evaluate the safety of the implantation of a new device for the treatment of anal fistulas. The short-term clinical efficacy was also assessed. METHODS: This study took place at a tertiary care university hospital. Patients with a complex anal fistula of cryptoglandular origin were enrolled in the study and were treated with insertion of the new device. All patients were evaluated by clinical and physical examination, including an endoanal ultrasound at the baseline, and then at the 2 wk and 1, 2, 3 and 6-mo follow-up visits. RESULTS: Morbidity, continence status, and success rate were the main outcome measures. Ten patients underwent the placement of the new device. The fistulas were transphincteric in eight patients and extrasphincteric in the remaining two. The median duration of the surgical procedure was 34.5(range, 27-42) min. Neither intra- nor postoperative complications occurred, and all patients were discharged the day after the procedure. At the 6-mo follow-up evaluation, the final success rate was 70%. Three failures were registered: a device expulsion(on the 10 th postoperative day), the persistence of inflammatory tissue around the fistula tract(at the 2-mo follow up), and the persistence of serum discharge(at the 6-mo follow up). No patient experienced any change incontinence, as assessed by the Cleveland Clinic Fecal Incontinence score. CONCLUSION: The technical procedure is simple and has low risk of perioperative morbidity. The pre- and post-operative continence status did not change in any of the patients. The initial results at the 6-mo follow up seem to be promising. However, a longer follow-up period and a larger sample size are needed to confirm these preliminary results.

关键词： Anal fistula Device Fistula plug Faecal incontinence Recurrence Endoanal ultrasound

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Avoiding the Avoidable:Towards a European Heat Waves Risk Governance

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International Journal of Disaster Risk Science 2011年第1期2卷 1-14页

作者： Wiebke Lass Armin Haas Jochen Hinkel carlo Jaeger Potsdam Institute for Climate Impact Research(PIK) D-14412 PotsdamGermany

The death toll of recent heat waves in developed countries has been remarkably high, contradicting the common assumption that high levels of economic and technological development automatically lead to lower vulnerability to weather extremes. Future climate change may further increase this vulnerability. In this article we examine some recent evidence of heat wave-related mortality and we conclude that while economic wealth and technological capacity might be a necessary condition for adequately coping with adverse climate change effects, they are not sufficient. Questions of awareness, preparedness, organizational issues, and actor networks have to be addressed in a proactive and focused manner in order to avoid future heat wave damages. We propose some practical consequences for heat wave adaptation measures by adopting a risk governance framework that can be universally applied, as it is sufficiently flexible to deal with the multi-level and often fragmented reality of existing coping measures.

关键词： weather wave consequences

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A Clustering Algorithm for Planning the Integration Process of a Large Number of Conceptual Schemas

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Journal of Computer Science & Technology 2015年第1期30卷 214-224页

作者： carlo Batini: Paola Bonizzoni Marco Comerio Riccardo Dondi Yuri Pirola Prancesco Salandra Department of Informatics Systems and Communication University of Milano-Bicocca Milan 20126 Italy Department of Human and Social Sciences University of Bergamo Bergamo 24129 Italy

When tens and even hundreds of schemas are involved in the integration process, criteria are needed for choosing clusters of schemas to be integrated, so as to deal with the integration problem through an efficient iterative process. Schemas in clusters should be chosen according to cohesion and coupling criteria that are based on similarities and dissimilarities among schemas. In this paper, we propose an algorithm for a novel variant of the correlation clustering approach that addresses the problem of assisting a designer in integrating a large number of conceptual schemas. The novel variant introduces upper and lower bounds to the number of schemas in each cluster, in order to avoid too complex and too simple integration contexts respectively. We give a heuristic for solving the problem, being an NP hard combinatorial problem. An experimental activity demonstrates an appreciable increment in the effectiveness of the schema integration process when clusters are computed by means of the proposed algorithm w.r.t, the ones manually defined by an expert.

关键词： conceptual schema schema integration clustering

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Diabetes mellitus and Parkinson's disease:dangerous liaisons between insulin and dopamine

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Neural Regeneration Research 2022年第3期17卷 523-533页

作者： Angela De Iuliis Ennio Montinaro Giuseppe Fatati Mario Plebani carlo Colosimo Department of Medicine-DiMED University of PadovaItaly Department of Neurology Santa Maria University HospitalTerniItaly Italian Obesity Network TerniItaly Department of Medicine-DiMED University of PadovaPadovaItaly/Department of Laboratory Medicine-Hospital of PadovaPadovaItaly

The relationship between diabetes mellitus and Parkinson's disease has been described in several epidemiological studies over the 1960 s to *** studies have shown the possible functional link between insulin and dopamine,as there is strong evidence demonstrating the action of dopamine in pancreatic islets,as well as the insulin effects on feeding and cognition through central nervous system mechanism,largely independent of glucose *** used for the treatment of type 2 diabetes mellitus appear to be promising candidates for symptomatic and/or disease-modifying action in neurodegenerative diseases including Parkinson's disease,while an old dopamine agonist,bromocriptine,has been repositioned for the type 2 diabetes mellitus *** review will aim at reappraising the different studies that have highlighted the dangerous liaisons between diabetes mellitus and Parkinson's disease.

关键词： dopamine GLP-1 insulin Parkinson's disease type 2 diabetes mellitus

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Growth and low-energy electron microscopy characteri- zation of monolayer hexagonal boron nitride on epitaxial cobalt

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Nano Research 2013年第5期6卷 335-347页

作者： carlo M. Orofeo Satoru Suzuki Hiroyuki Kageshima Hiroki Hibino NTT Basic Research Laboratories NTT Corporation A tsugi Kanagawa 243-0198 Japan

Low-energy electron microscopy （LEEM） has been used to study the structure, initial growth orientation, growth progression, and the number of layers of atomically thin hexagonal boron nitride （h-BN） films. The h-BN films are grown on heteroepitaxial Co using chemical vapor deposition （CVD） at low pressure. Our findings from LEEM studies include the growth of monolayer film having two, oppositely oriented, triangular BN domains commensurate with the Co lattice. The growth of h-BN appears to be self-limiting at a monolayer, with thicker domains only appearing in patches, presumably initiated between domain boundaries. Reflectivity measurements of the thicker h-BN films show oscillations resulting from the resonant electron transmission through quantized electronic states of the h-BN films, with the number of minima scaling up with the number of h-BN layers. First principles density functional theory （DFT） calculations show that the positions of oscillations are related to the electronic band structure of h-BN.

关键词： chemical vapor deposition cobalt domain boundaries hexagonal boron nitride low-energy electronmicroscopy (LEEM)

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Synthesis of Large Area, Homogeneous, Single Layer Graphene Films by Annealing Amorphous Carbon on Co and Ni

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Nano Research 2011年第6期4卷 531-540页

作者： carlo M. Orofeo Hiroki Ago Baoshan Hu Masaharu Tsuji Graduate School of Engineering Sciences Kyushu University Kasuga Fukuoka 816-8580 Japan Institute for Materials Chemistry and Engineering Kyushu University Kasuga Fukuoka 816-8580 Japan

The synthesis of large area, homogenous, single layer graphene on cobalt （Co） and nickel （Ni） is reported. The process involves vacuum annealing of sputtered amorphous carbon （a-C） deposited on Co/sapphire or Ni/sapphire substrates. The improved crystallinity of the metal film, assisted by the sapphire substrate, proves to be the key to the quality of as-grown graphene film. The crystallinity of the Co and Ni metal films was improved by sputtering the metal at elevated temperature as was verified by X-ray diffraction （XRD）. After sputtering of a-C and annealing, large area, single layer graphene that occupies almost the entire area of the substrate was produced. With this method, 100 mm2-area single layer graphene can be synthesized and is limited only by the substrate and vacuum chamber size. The homogeneity of the graphene film is not dependent on the cooling rate, in contrast to syntheses using polycrystalline metal films and conventional chemical vapor deposition （CVD） growth. Our facile method of producing single layer graphene on Co and Ni metal films should lead to large scale graphene-based applications.

关键词： Single layer graphene amorphous carbon epitaxial metal annealing

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