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111.
Understanding how animals navigate complex environments is a fundamental challenge in biology and a source of inspiration for the design of autonomous systems in engineering. Animal orientation and navigation is a complex process that integrates multiple senses, whose function and contribution are yet to be fully clarified. Here, we propose a data-driven mathematical model of adult zebrafish engaging in counter-flow swimming, an innate behavior known as rheotaxis. Zebrafish locomotion in a two-dimensional fluid flow is described within the finite-dipole model, which consists of a pair of vortices separated by a constant distance. The strength of these vortices is adjusted in real time by the fish to afford orientation and navigation control, in response to of the multi-sensory input from vision, lateral line, and touch. Model parameters for the resulting stochastic differential equations are calibrated through a series of experiments, in which zebrafish swam in a water channel under different illumination conditions. The accuracy of the model is validated through the study of a series of measures of rheotactic behavior, contrasting results of real and in-silico experiments. Our results point at a critical role of hydromechanical feedback during rheotaxis, in the form of a gradient-following strategy. 相似文献
112.
Maria Scarselli Laura Santini Sara Dragonetti Silvana Savino Maurizio Comanducci Giacomo Romagnoli Lucia Banci Rino Rappuoli 《Journal of molecular biology》2009,386(1):97-41775
The factor H binding protein (fHbp) is a 27-kDa membrane-anchored lipoprotein of Neisseria meningitidis that allows the survival of the bacterium in human plasma; it is also a major component of a universal vaccine against meningococcus B.In this study, we used nuclear magnetic resonance spectroscopy, mutagenesis, and in silico modeling to map the epitope recognized by MAb502, a bactericidal monoclonal antibody elicited by fHbp. The data show that the antibody recognizes a conformational epitope within a well-defined area of the immunodominant C-terminal domain of the protein that is formed by two loops connecting different β-strands of a β-barrel and a short α-helix brought in spatial proximity by the protein folding. The identification of the protective epitopes of fHbp is an important factor for understanding the mechanism(s) of an effective immune response and provides valuable guidelines for designing variants of the protein able to induce broadly protective immunity. 相似文献
113.
114.
Marian Suarez-Gestal Manuel Calaza Em?ke Endreffy Rudolf Pullmann Josep Ordi-Ros Gian Domenico Sebastiani Sarka Ruzickova Maria Jose Santos Chryssa Papasteriades Maurizio Marchini Fotini N Skopouli Ana Suarez Francisco J Blanco Sandra D'Alfonso Marc Bijl Patricia Carreira Torsten Witte Sergio Migliaresi Juan J Gomez-Reino Antonio Gonzalez 《Arthritis research & therapy》2009,11(3):R69
Introduction
We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.Methods
We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections.Results
A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.Conclusions
Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect. 相似文献115.
Di Giacomo AM Danielli R Calabrò L Bertocci E Nannicini C Giannarelli D Balestrazzi A Vigni F Riversi V Miracco C Biagioli M Altomonte M Maio M 《Cancer immunology, immunotherapy : CII》2011,60(4):467-477
Aim of study
To evaluate the feasibility of ipilimumab treatment for metastatic melanoma outside the boundaries of clinical trials, in a setting similar to that of daily practice.Methods
Ipilimumab was available upon physician request in the Expanded Access Programme for patients with life-threatening, unresectable stage III/IV melanoma who failed or did not tolerate previous treatments and for whom no therapeutic option was available. Induction treatment with ipilimumab 10?mg/kg was administered intravenously every 3?weeks, for a total of 4 doses, with maintenance doses every 12?weeks based on physicians?? discretion and clinical judgment. Tumors were assessed at baseline, Week 12, and every 12?weeks thereafter per mWHO response criteria, and clinical response was scored as complete response (CR), partial response (PR), stable disease (SD), or progressive disease. Durable disease control (DC) was defined as SD at least 24?weeks from the first dose, CR, or PR.Results
Disease control rate at 24 and 60?weeks was 29.6% and 15%, respectively. Median overall survival at a median follow-up of 8.5?months was 9?months. The 1- and 2-year survival rates were 34.8% and 23.5%, respectively. Changes in lymphocyte count slope and absolute number during ipilimumab treatment appear to correlate with clinical response and survival, respectively. Adverse events were predominantly immune related, manageable, and generally reversible. One patient died from pancytopenia, considered possibly treatment related.Conclusion
Ipilimumab was a feasible treatment for malignant melanoma in heavily pretreated, progressing patients. A sizeable proportion of patients experienced durable DC, including benefits to long-term survival. 相似文献116.
Functional heterogeneity of vaccine-induced CD8(+) T cells 总被引:5,自引:0,他引:5
Monsurrò V Nagorsen D Wang E Provenzano M Dudley ME Rosenberg SA Marincola FM 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5933-5942
The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8(+) T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 +/- 3,600 x 10(6) CD8(+) T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA(+)CD27(+) (14 +/- 2.6% of tHLA-staining T cells), naive; CD45RA(-)CD27(+) (14 +/- 3.2%), memory; CD45RA(+)CD27(-) (43 +/- 6%), effector; and CD45RA(-)CD27(-) (30 +/- 4.1%), memory/effector. The majority of tHLA(+)CD8(+) T cells displayed an effector, CD27(-) phenotype (73%). However, few expressed perforin (17%). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin(+) (84 +/- 3.6%; by paired t test, p < 0.001) and CD27(+) (from 28 to 67%; by paired t test, p = 0.01) tHLA(+) T cells. This conversion probably represented a change in the functional status of tHLA(+) T cells rather than a preferential expansion of a CD27(+) (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA(+)CD27(-)). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation. 相似文献
117.
Hui Yang Philippe Ciais Maurizio Santoro Yuanyuan Huang Wei Li Yilong Wang Ana Bastos Daniel Goll Almut Arneth Peter Anthoni Vivek K. Arora Pierre Friedlingstein Vanessa Harverd Emilie Joetzjer Markus Kautz Sebastian Lienert Julia E. M. S. Nabel Michael O'Sullivan Stephen Sitch Nicolas Vuichard Andy Wiltshire Dan Zhu 《Global Change Biology》2020,26(7):3997-4012
Gaps in our current understanding and quantification of biomass carbon stocks, particularly in tropics, lead to large uncertainty in future projections of the terrestrial carbon balance. We use the recently published GlobBiomass data set of forest above‐ground biomass (AGB) density for the year 2010, obtained from multiple remote sensing and in situ observations at 100 m spatial resolution to evaluate AGB estimated by nine dynamic global vegetation models (DGVMs). The global total forest AGB of the nine DGVMs is 365 ± 66 Pg C, the spread corresponding to the standard deviation between models, compared to 275 Pg C with an uncertainty of ~13.5% from GlobBiomass. Model‐data discrepancy in total forest AGB can be attributed to their discrepancies in the AGB density and/or forest area. While DGVMs represent the global spatial gradients of AGB density reasonably well, they only have modest ability to reproduce the regional spatial gradients of AGB density at scales below 1000 km. The 95th percentile of AGB density (AGB95) in tropics can be considered as the potential maximum of AGB density which can be reached for a given annual precipitation. GlobBiomass data show local deficits of AGB density compared to the AGB95, particularly in transitional and/or wet regions in tropics. We hypothesize that local human disturbances cause more AGB density deficits from GlobBiomass than from DGVMs, which rarely represent human disturbances. We then analyse empirical relationships between AGB density deficits and forest cover changes, population density, burned areas and livestock density. Regression analysis indicated that more than 40% of the spatial variance of AGB density deficits in South America and Africa can be explained; in Southeast Asia, these factors explain only ~25%. This result suggests TRENDY v6 DGVMs tend to underestimate biomass loss from diverse and widespread anthropogenic disturbances, and as a result overestimate turnover time in AGB. 相似文献
118.
Symbiotic nitrogen fixation is carried out in specialized organs, the nodules, whose formation is induced on leguminous host plants by bacteria belonging to the family Rhizobiaceae. Nodule development is a complex multistep process, which requires continued interaction between the two partners and thus the exchange of different signals and metabolites. NH4+ is not only the primary product but also the main regulator of the symbiosis: either as ammonium and after conversion into organic compounds, it regulates most stages of the interaction, from the production of nodule inducers to the growth, function, and maintenance of nodules. This review examines the adaptation of bacterial NH4+ metabolism to the variable environment generated by the plant, which actively controls and restricts bacterial growth by affecting oxygen and nutrient availability, thereby allowing a proficient interaction and at the same time preventing parasitic invasion. We describe the regulatory circuitry responsible for the downregulation of bacterial genes involved in NH4+ assimilation occurring early during nodule invasion. This is a key and necessary step for the differentiation of N2-fixing bacteroids (the endocellular symbiotic form of rhizobia) and for the development of efficient nodules. 相似文献
119.
Don C Lamb Karin Nienhaus Alessandro Arcovito Federica Draghi Adriana E Miele Maurizio Brunori G Ulrich Nienhaus 《The Journal of biological chemistry》2002,277(14):11636-11644
Fourier transform infrared (FTIR) spectroscopy in the CO stretch bands combined with temperature derivative spectroscopy (TDS) was used to characterize intermediate states obtained by photolysis of two sperm whale mutant myoglobins, YQR (L29(B10)Y, H64(E7)Q, T67(E10)R) and YQRF (with an additional I107(G8)F replacement). Both mutants assume two different bound-state conformations, A(0) and A(3), which can be distinguished by their different CO bands near 1965 and 1933 cm(-1). They most likely originate from different conformations of the Gln-64 side chain. Within each A substate, a number of photoproduct states have been characterized on the basis of the temperature dependence of recombination in TDS experiments. Different locations and orientations of the ligand within the protein can be distinguished by the infrared spectra of the photolyzed CO. Recombination from the primary docking site, B, near the heme dominates below 50 K. Above 60 K, ligand rebinding occurs predominantly from a secondary docking site, C', in which the CO is trapped in the Xe4 cavity on the distal side, as shown by crystallography of photolyzed YQR and L29W myoglobin CO. Another kinetic state (C") has been identified from which rebinding occurs around 130 K. Moreover, a population appearing above the solvent glass transition at approximately 180 K (D state) is assigned to rebinding from the Xe1 cavity, as suggested by the photoproduct structure of the L29W sperm whale myoglobin mutant. For both the YQR and YQRF mutants, rebinding from the B sites near the heme differs for the two A substates, supporting the view that the return of the ligand from the C', C", and D states is not governed by the recombination barrier at the heme iron but rather by migration to the active site. Comparison of YQR and YQRF shows that access to the Xe4 site (C') is severely restricted by introduction of the bulky Phe side chain at position 107. 相似文献
120.