514 research outputs found

    Signaling in natural killer cells: SHIP, 2B4 and the Kinome

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    The NK cell is a large granular lymphocyte that plays a key role in protecting the body against numerous pathogens including parasites, intracellular bacteria, viral infections, as well as showing anti-tumor activity and playing a role in the rejection of allogeneic BM. Unlike other lymphocytic cell types, that utilize rearranging receptors, NK cells are regulated by a complex array of germ line encoded activating and inhibitory receptors. NK cells are often described as a front line or rapid defense given their response to stimuli can be immediate, although they also maintain functions that extend their role well into the adaptive immune system. Inhibitory receptors that recognize MHC class I molecules regulate NK cell responses and self-tolerance. Recent evidence indicates self-ligands not present in the MHC locus can also modulate NK function. We previously demonstrated that the NK receptor repertoire is disrupted by SHIP-deficiency. Here we show that an inhibitory receptor, 2B4, that recognizes an MHC-independent ligand is over expressed in NK cells of SHIP-/- mice at all stages of NK development and differentiation. Overexpression of 2B4 compromises key cytolytic NK functions, including killing of allogeneic, tumor and viral targets. These results demonstrate that in SHIP-/- NK cell 2B4 is the dominant inhibitory receptor. We then furthered this finding by examining the molecular basis of 2B4 dominance. We show that in SHIP-/- NK cells there is increased 2B4 expression as well as a strong bias towards the 2B4L isoform. We have also identified a greater than tenfold increase in SHP1 recruitment to 2B4. Consistent with this SHP1 over recruitment,both a broad and a selective SHP1 inhibitor restore SHIP-/- NK killing of complex targets.Through this study we have identified the molecular mechanism of 2B4 receptor dominance as SHP1 over-recruitment.In addition we have utilized protein array technology to explore NK signaling through the determination of the NK kinome. To this end we have been able to identify multiple pathways that may mark crucial differences between the mature and immature NK cell

    The genomic organisation of the tra/trd locus validates the peculiar characteristics of dromedary δ-chain expression

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    The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) account for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage of the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR α (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site

    Aphanocladium album by via sub-irrigation in the control of Pyrenochaeta lycopersici and Meloidogyne incognita on tomato in a plastic-house

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    AbstractTwo experiments were carried out to assess the efficacy of different chemicals (azoxystrobin, fosthiazate, metham-sodium) and of the chitinolytic fungus Aphanocladium album (isolate MX-95), that could be alternatives to methyl bromide, against the soil borne pathogen Pyrenochaeta lycopersici and the root-knot nematode Meloidogyne incognita on tomato in a plastic house in southern Italy. In the first trial, the treatments were azoxystrobin (1.25 l a.i. /ha), fosthiazate (1.5 l a.i. /ha) and biological control agent Aphanocladium album isolate MX-95 (2.5 l/plot at 2×107 CFU/ml; plot surface 96 m2). In the second experiment, treatments were metham-sodium (1000 l c.p./ha) and A. album (5 l/plot at 1×107 CFU/ml). In both trials, chemicals and the fungus were applied by via sub-irrigation. Satisfactory control of the corky root and the root-knot nematode attack and a significant yield increase were obtained by application of azoxystrobin, fosthiazate and metham-sodium. A significant reduction of M. incognita soil population density occurred in plots treated with A. album. Also, high positive correlations were found between the symptoms caused on tomato roots by M. incognita and P. lycopersici

    Comparing the first and the second waves of COVID-19 in Italy: differences in epidemiological features and CT findings using a semi-quantitative score

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    Purpose: CT findings of hospitalized COVID-19 patients were analyzed during both the first and the second waves of the pandemic, in order to detect any significant differences between the two groups. Methods: In this observational, retrospective, monocentric study, all hospitalized patients who underwent CT for suspected COVID-19 pneumonia from February 27 to March 27, 2020 (first wave) and from October 26 to November 24, 2020 (second wave) were enrolled. Epidemiological data, radiological pattern according to the RSNA consensus statement and visual score extension using a semi-quantitative score were compared. Results: Two hundred and eleven patients (mean age, 64.52 years ± 15.14, 144 males) were evaluated during the first wave while 455 patients (mean age, 68.26 years ± 16.34, 283 males) were studied during the second wave. The same prevalence of patterns was documented in both the first and the second waves (p = 0.916), with non-typical patterns always more frequently observed in elderly patients, especially the “indeterminate” pattern. Compared to those infected during the first wave, the patients of the second wave were older (64.52 vs.68.26, p = 0.005) and presented a slightly higher mean semi-quantitative score (9.0 ± 2.88 vs. 8.4 ± 3.06, p = 0.042). Age and semi-quantitative score showed a positive correlation (r = 0.15, p = 0.001). Conclusions: There was no difference regarding CT pattern prevalence between the first and the second waves, confirming both the validity of the RSNA consensus and the most frequent radiological COVID-19 features. Non-typical COVID-19 features were more frequently observed in older patients, thus should not be underestimated in the elderly population

    MICROPILES TRIPODS SHIELDS (MTS) AS UNCONVENTIONAL BREAKERS FOR THE CONTROL OF MODERATELY RAPID EARTHFLOWS (SASSI NERI LANDSLIDE, NORTHERN APENNINES)

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    The paper deals with the idea, design and implementation of unconventional one-of-a-kind Micropiles Tripods Shields (MTS) intended to break and decelerate moderately rapid earthflows surges in the track zone of the Sassi Neri landslide (Nure Valley, Northern Apennines, Province of Piacenza, Italy). The MTS are inspired to floating anchors and “chevaux de fries” used in wartime. The basic elements are tripods of 193 mm diameter steel micropiles laid out at triangle, driven into the stable bedrock and emerging some meters aboveground. Each tripod consists of a vertical upslope central pile and two lateral oblique piles, linked by two transversal beams and connection plates aboveground. Multiple tripods are spaced along transversal rows to form Micropiles Tripods Shields (MTS) to advancing earthflows. The design of MTS has been based on field investigations such as boreholes and geophysics, that indicated a limited thickness of landslide deposits in the track zone where MTS have been installed. The forces resulting from active earthflows fronts have been estimated both with geotechnical and hydraulic computations. The analysis of vertical and transversal forces as well as bending moments acting on a single tripod versus the characteristic resistances was carried out using a bi-dimensional scheme with finite-elements software Plaxis, that indicated that the stress levels were compatible with the structural resistance of the tripods. The construction of MTS took place in 2018, involving working site preparation with partial lime-treatment of the surficial layers, underground micropiles drilling and installation, aboveground micropiles welding, tripods completion with connection beams and plates. Some tripods have been instrumented with load cells for monitoring earth pressures against micropiles, electric transducers for groundwater monitoring next to the piles, tiltmeters for tripods rotations and a total station for slope and tripods movements monitoring. Results show that the acceleration of slope movements corresponds to a generalized increase of pore water pressure at all the monitored tripods and to temporary slight tilting of the tripods which has so far being fully recovered when the landside slowed down and pressure decreased. This pioneering application indicates that once the characteristics of the earthflows are carefully considered, the depth to the bedrock in the installation zone is limited, and the logistical conditions in the field during construction are adequate, the MTS can be taken into consideration as a possible unconventional solution to break down and control moderately rapid earthflow

    Evolution of the T-cell receptor (TR) Loci in the adaptive immune response: The tale of the TRG locus in mammals

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    T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response

    The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla

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    The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda, and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC "cassettes", each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the γ-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5' end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner
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