171,143 research outputs found
Coroichlorops yungas Sabrosky & Paganelli
No full text<i>Coroichlorops yungas</i> (Sabrosky & Paganelli), 1984 <p>(Figs. 1–4)</p> <p> <i>Coroichlorops yungas</i> (Sabrosky & Paganelli), 1984: 35 (<i>Chlorops</i>; nom. nov. for <i>maculata</i> Duda, 1930). (Paganelli 2002: 37, figs. 100–106). Type-locality: Bolivia, Coroico. Holotype ♂ with label: (1) printed with handwritten inscriptions on green paper: “ Bolivia | 30.xi.06 | Yungas von Coroico | 1800m ” [SNSD]. Refs.: Sabrosky & Paganelli 1984; Paganelli 2002. <i>maculata</i> Duda, 1930: 124 (<i>Chlorops</i>; preocc. Walker, 1849).</p> <p> <i>maculosa</i> Duda, 1931: 171 (<i>Chlorops</i>; error for <i>maculata</i> Duda, 1930, preocc. Loew, 1872).</p> <p> <b>Comments</b>. The holotype of <i>C. yungas</i> is well preserved, with no missing parts. Externally <i>C. yungas</i> is very similar to <i>C. plaumanni</i>. Nevertheless, <i>C. yungas</i> presents a wide shallow sulcus in the ocellar triangle, a long sensorial pit on the first flagellomere, a complete facial carina, and almost indistinct scutum stripes. No additional specimens of <i>C. yungas</i> have been found in the collections studied.</p>Published as part of <i>Riccardi, Paula Raile & Amorim, Dalton De Souza, 2016, Revision of the Neotropical genus Coroichlorops Paganelli 2002 (Diptera: Chloropidae), pp. 435-443 in Zootaxa 4093 (3)</i> on page 436, DOI: 10.11646/zootaxa.4093.3.9, <a href="http://zenodo.org/record/262631">http://zenodo.org/record/262631</a>
Congresso Nazionale SIGENP.Valutazione della densità minerale in bambini affetti da malattia infiammatoria cronica intestinale. M. Paganelli, C Albanese, et al.
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Fas Pathway of Cell Death and B Cell Dysregulationin SLE
No full textSystemic lupus erythematosus (SLE) is a generalized autoimmune disease affecting several organ systems, characterized by the presence of a vast array of autoantibodies, characteristically directed to nuclear antigens (ANA).
The heterogeneity of clinical manifestations and the
disease's unpredictable course characterized by flares and remissions are very
likely a reflection of heterogeneity at the origin of disease, with a final
common pathway leading to loss of tolerance to nuclear antigens. Impaired
clearance of immune complexes and apoptotic material and production of
autoantibodies have long been recognized as major pathogenic events
Apoptotic defects underlie some models of autoimmune diseases, and they have been proposed in the pathogenesis of SLE) a prototypic autoimmune disorder
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease
characterized by the production of high-titer IgG autoantibodies directed against
nuclear autoantigens. Type I interferon (IFN-I) has been shown to play a
pathogenic role in this disease.
Cell death as driving force for autoantibodies production
phagocytes engulf dead cells, which are
recognized as dead by virtue of a characteristic "eat me" signal exposed on their
surface. Inefficient engulfment of dead cells activates
the immune system, causing disease such as systemic lupus erythematosus, The molecular details of these processes has been recently superbly reviewed in Cell, 2010.
During apoptosis, the asymmetric distribution of phospholipids (PS) of the
plasma membrane gets lost and PS is translocated to the outer leaflet of the
plasma membrane. There, PS acts as one major "eat me" signal that ensures
efficient recognition and uptake of apoptotic cells by phagocytes. PS recognition
of activated phagocytes induces the secretion of anti-inflammatory cytokines like
interleukin-10
Accumulation of dead cells containing nuclear autoantigens in sites of immune selection may provide survival signals for autoreactive B-cells. The production of antibodies against nuclear
structures determines the initiation of chronic autoimmunity in systemic lupus erythematosus. Various
soluble molecules and biophysical properties of the surface of apoptotic cells
play significant roles in the appropriate recognition and further processing of
dying and dead cells. We exemplarily discuss how Milk fat globule epidermal
growth factor 8 (MFG-E8), biophysical membrane alterations, High mobility group
box 1 (HMGB1), C-reactive protein (CRP), and anti-nuclear autoantibodies may
contribute to the etiopathogenesis of the disease.
Over 50 years ago, the identification of antibodies to
double-stranded (ds) DNA (?). Whilst widely regarded as synonymous with patients who
have systemic lupus erythematosus (SLE), doubts have been raised about their
significance whether they are merely part of
the spectrum of anti-nucleosome antibodies. There is increasing evidence that in systemic lupus erythematosus, nucleosomes,
the basic chromatin component, represent both a driving immunogen and a major in
vivo target for antibodies. Either a disturbed apoptosis or a reduced clearance
of apoptotic cells by phagocytes may lead to an increased exposure of apoptotic
nucleosomes to the immune system. These nucleosomes, which have been cleaved and
modified during the process of apoptosis, escape normal clearance.
Immune complexes containing DNA and RNA are responsible for disease
manifestations found in patients with systemic lupus erythematosus (SLE). B cells
contribute to SLE pathology through BCR recognition of endogenous DNA- and RNA-
associated autoantigens to production
of class-switched DNA- and RNA-reactive autoantibodies, contributing to an
inflammatory amplification loop characteristic of the disease. Intriguingly, self-DNA
and RNA are typically non-stimulatory for TLR9/7 - engagement of the type I IFN receptor promotes B cell activation by
weakly stimulatory DNA and RNA TLR ligands. Anti-nucleosome antibodies were
positive in 40 (97.6%) patients with active SLE, had a stronger correlation than anti-dsDNA antibodies with SLEDAI score. Anti-nucleosome antibodies test is highly sensitive and specific for
the diagnosis of SLE, There
mouse models of autoimmune disorders where mutations of the lpr and gld genes lead to defective expression of Fas and respectively, FasL, resulting in the persistence of autoreactive immune cells due to deficiency of their elimination through apoptotic mechanisms
The Fas/FasL pathway of apoptosis in SLE
Fas is a 43 kDa glycoprotein molecule which is involved in inducing apoptosis in
both B and T lymphocytes. In the murine MRL/Ipr-Ipr model of systemic lupus
erythematosus (SLE), the lymphoproliferation (lpr) mutation results in defective
transcription of the gene that codes for the Fas protein. MRL mice which carry
the homozygous recessive Ipr mutation develop a severe early-onset genetically
predetermined autoimmune syndrome. Susceptibility to SLE is found to be associated
with many genes, one of which
is APO-1/Fas gene, which is present on chromosome 10 in humans. The APO-1/Fas
promoter contains consensus sequences for binding of several transcription
factors that affect the intensity of Fas expression in cells. The mutations in
the APO-1/Fas promoter are associated with risk and severity in various
autoimmune diseases. A decreased rate of apoptosis, possibly related to elevated levels of soluble Fas (sFas) which can inhibit Fas mediated apoptosis of lymphocytes.
In overwhelming majority of situations alterations in Fas and FasL expression are
viewed in frames of Fas-mediated apoptosis. In the present work we tested a
possible involvement of Fas-ligand-mediated "reverse signaling" in pathogenesis
of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus
erythematosus (SLE). We show that high level of sFas in RA patient blood
correlates with a high activity of disease; in SLE patients with elevated sFas
level there was a correlation between sFas concentration and leucopenia, and
tissue and organ damage. We showed for the first time that at high concentrations
in serum sFas is present in oligomeric form. Oligomeric sFas demonstrated
cytotoxicity in lymphocyte primary culture and in transformed cells, while
non-toxic recombinant Fas-ligand partially blocked this effect.
Levels of sFas correlated with the percentages of
activated B cells defined as CD20(+)CD38(+) cells. Serum levels of
sFas correlate with percentages of activated B cells but not with that of
activated T cells.
There was a significant correlation between serum concentrations of sFAS and
IL-18 in SLE patients
sFas and alfa-TNF serum levels are increased in SLE patients. sFas
levels seems to be secondary to alfa-TNF action, which is enhanced in
inflammatory conditions such as SLE. Bcl-2 antigen expression and IL-10 serum
levels are related to the maintenance of SLE activity. These alterations may
interfere with the apoptotic process
Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family, and
its receptor Fas are critical for the shutdown of chronic immune responses and
prevention of autoimmunity. Accordingly, mutations in their genes cause severe
lymphadenopathy and autoimmune disease in mice and humans. FasL function is
regulated by deposition in the plasma membrane and metalloprotease-mediated
shedding. mFasL is essential
for cytotoxic activity and constitutes the guardian against lymphadenopathy,
autoimmunity and cancer, whereas excess sFasL appears to promote autoimmunity
Lymphocytes from aged autoimmune MRL/lpr mice overexpress Fas ligand (FasL), and
are cytotoxic against Fas+ target cells. This cytotoxic potential is only partly
due to FasL, as wild-type MRL+/+ lymphocytes are not able to kill Fas+ targets
after induction of FasL.
Type I Interferons and apoptosis
Type I IFN (IFN-I) was firstly described in 1957 as a soluble factor responsible
for viral resistance in vitro. IFN-I can be considered a "director" of protective immune responses. The recent finding of the so-called interferon signature in patients suffering from
different autoimmune diseases has underlined its possible role in the
pathogenesis of these diseases.
Plasmacytoid dendritic cells (pDCs) are specialized type I IFN producers
significantly enhance autoreactive B cell proliferation, autoantibody production,
and survival in response to TLR and BCR stimulation. . IFNAR2-/- B
cells failed to upregulate nucleic acid-sensing
Toll-like receptors TLR7 as well as TLR9 expression in response to IFN-I,
and effector responses to TLR7 and TLR9 agonists were significantly decreased as
compared to B cells from WT mice following treatment with IFN-alpha.
In addition, serum levels of interferon-alpha
(IFN-alpha) increase in parallel with the Fas-dependent cytotoxic potential of
lymphocytes from MRL/lpr mice as they age. To understand the mechanisms
underlying these observations, combined suppression subtractive hybridization
(SSH) and RT-PCR were used to study differential gene expression in splenocytes
from MRL/lpr mice compared with splenocytes from MRL+/+ mice. Twenty-two genes
were upregulated transcriptionally in MRL/lpr splenocytes compared with their
MRL+/+ counterparts. Furthermore, 9 of these genes were also upregulated after
treatment of MRL/lpr splenocytes with IFN-alpha, and 4 were strongly
downregulated. MRL/lpr lymphocytes were also found to be hyperresponsive to
IFN-alpha.
Nagafuchi H, Wakisaka S, Takeba Y, Takeno M, Sakane T, Suzuki N.
Aberrant expression of Fas ligand on anti-DNA autoantibody secreting B
lymphocytes in patients with systemic lupus erythematosus: "immune
privilege"-like state of the autoreactive B cells.
Suzuki N, Ichino M, Mihara S, Kaneko S, Sakane T.
Inhibition of Fas/Fas ligand-mediated apoptotic cell death of lymphocytes in
vitro by circulating anti-Fas ligand autoantibodies in patients with systemic
lupus erythematosus.Arthritis Rheum. 1998
A novel subset of memory B cells is enriched in autoreactivity and correlates
with adverse outcomes in SLE.Nicholas MW,2008.
CD19(hi) B cells have elevated CXCR3 levels and chemotax in
response to its ligand CXCL9. Thus, CD19(hi) B cells are precursors to anti-self
PCs, and identify an SLE patient subset likely to experience poor clinical
outcomes.
Quantitative genetic variation in CD19 expression correlates with autoimmunity.[J Immunol. B Lymphocyte signaling established by the CD19/CD22 loop regulates autoimmunity Warnatz K, Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia
Although IFN-α was reported to promote the survival of peripheral B-lymphocytes via the PI3-kinase-Akt pathway, the triggered signalling pathways involved in the protection of B cell from apoptosis need to be clarified. Using flow cytometry and western blot analysis, we have found that type 1 IFNs (IFN-α/β) protect human B cells in culture from spontaneous apoptosis and from apoptosis mediated by anti-CD95 agonist, in a dose- and time-dependant manner. IFN-α/β-mediated anti-apoptotic effect on human B cells was totally abrogated by blockade of IFNR1 chain. Our data indicate that PI3Kδ, Rho-A, NFκB and Bcl-2/BclXL are active downstream of IFN receptors and are the major effectors of IFN-α/β-rescued B cells from apoptosis. Furthermore, immunohistochemical results show marked reduction in numbers of CD20 positive B cell in both spleen and Peyer’s patches from mice treated with anti-IFNR1 blocking antibody compared with control group. Moreover, ultrastructural observations of these organs show an obvious increase in apoptotic cells from mice treated with anti-IFNR1 blocking antibody. Our results provide more details about the triggered signalling pathways and the phosphorylation cascade which are involved in the protection of B cell from apoptosis after treatment with IFN-α/β.
at high concentrations in serum sFas is present in oligomeric form. Oligomeric sFas demonstrated cytotoxicity in lymphocyte primary culture and in transformed cells, while non-toxic recombinant Fas-ligand partially blocked this effect - a possible involvement of Fas-ligand-mediated “reverse signaling” in pathogenesis of autoimmune diseases
In healthy controls, more memory than naive T lymphocytes underwent apoptosis. By contrast, in patients with SLE, more naive T cells underwent apoptosis with TNFalpha (p<0.01). Enhanced apoptosis of T cells in SLE was independent of disease activity or medication. Finally, inhibition experiments showed that apoptosis in the presence of TNFalpha was only partly blocked with anti-Fas ligand (FasL) antibody
mFas expression levels were significantly higher (P < 0.01) among SLE patients than those in healthy controls, the expression levels had a positive (r = 0.381, P < 0.01) correlation with the early apoptosis rate of PBLs in SLE patients
SLE serum induce classical caspase-dependent apoptosis, and this was independent of death receptor pathways.
results demonstrate increasing serum concentrations of the soluble molecules sFas and sFasL during the first days after birth, indicating possibly a gradual decrease of apoptosis in early neonatal life.
Neutrophil apoptosis was significantly increased in patients with juvenile-onset SLE as compared with the noninflammatory controls Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile-onset SLE,
Lymphocytes from aged autoimmune MRL/lpr mice overexpress Fas ligand (FasL), and
are cytotoxic against Fas+ target cells. This cytotoxic potential is only partly
due to FasL, as wild-type MRL+/+ lymphocytes are not able to kill Fas+ targets
after induction of FasL. In addition, serum levels of interferon-alpha
(IFN-alpha) increase in parallel with the Fas-dependent cytotoxic potential of
lymphocytes from MRL/lpr mice as they age
MRL/lpr lymphocytes overexpressed mRNA for the IFN-alpha
receptor (IFNAR-1 and IFNAR-2) chains of the IFN-alpha/beta receptor and
exhibited high endogenous levels of both Stat1 and phosphorylated Stat1 proteins.
Lymphocytes from young MRL/lpr mice, with low Fas-dependent cytotoxic activity,
were found to become highly cytotoxic against Fas+ targets after treatment with
IFN-alpha. These data suggest that IFN-alpha plays an important role in the
physiopathology of the systemic lupus erythematosus (SLE)-like syndrome that
occurs in MRL/lpr mice.
B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice.
A novel subset of memory B cells is enriched in autoreactivity and correlates
with adverse outcomes in SLE.
of circulating memory B cells with >2-fold higher levels of CD19. We
show here that the presence of CD19(hi) B cells correlates with long-term adverse outcomes. These B cells do not appear anergic, as they exhibit high basal levels of phosphorylated Syk and ERK1/2, signal transduce in response to BCR crosslinking, and can become plasma cells (PCs) in vitro. Autoreactive anti-Smith (Sm) B cells are enriched
B cell functions are under the regulation of
B cell antigen receptor (BCR)-induced signals and by specialized cell surface
coreceptors, or "response regulators", which inform B cells of their
microenvironment. These response regulators include CD19 and CD22. Importantly, this "CD19/CD22 loop" is significantly related to an autoimmune phenotype in mice. Thus, the CD19/CD22 loop may be a potential therapeutic target
B cell phenotypes in SLE
Regulatory B cells that produce IL-10 are now recognized as an important
component of the immune system . B10 progenitor (B10pro) cells have also been
identified within the spleen CD1d(hi)CD5(+)CD19(hi) B-cell subset that B cells exert their regulatory role through the production of interleukin-10
(IL-10) by either B-1, marginal zone (MZ), or transitional 2-MZ precursor B-cell
subsets. We have recently found that IL-10-producing regulatory B cells
predominantly localize within a rare CD1d(hi)CD5(+) B-cell subset that shares
cell surface markers with both B-1 and MZ B cells. We have labeled this specific
subset of regulatory B cells as B10 cells
deficient for CD19 (CD19(-/-) NZB/W mice), an important protective role for regulatory B10
cells in this systemic autoimmune disease
B cell depletion initiated in 4-wk-old mice hastened disease onset, which paralleled depletion of the IL-10-producing regulatory B cell subset called B10 cells
SLE as the result of defects both in apoptosis control and B cell regulatio
Hydroformylation of Cinnamic Acid Derivatives Catalyzed by Rhodium Complexes
No full textThe hydroformylation of methyl cinnamate catalysed by various rhodium complexes affords the aldehyde 1a with good chemo- and regio-selectivity, while in the case of methyl p-chlorocinnamate the predominant reaction is the substrate hydrogenation. Higher yields of the desired aldehydes 1a and 1b are obtained by hydroformylation of the cinnamaldehyde and p-chlorocinnamaldehyde diethylacetal, respectively, under the same reaction conditions. These aldehyde products are valuable drug precursors. © 1993
Hydroformylation of Olefins Catalyzed by Alkene Complexes of Platinum(0)
No full textIn the presence of methanesulfonic acid the platinum(0) complex [Pt(C2H4)(DPPB)] catalyses the hydroformylation of various olefins. In some cases there is quite good chemoselectivity and high regioselectivity towards n-aldehyde. © 1991
Designing synchronous belt transmissions with variable velocity ratio
No full textThe paper presents a new procedure to design a two-pulley synchronous belt transmission connecting, with no belt tensioner, two parallel-axis shafts with a variable velocity ratio. The procedure takes into account the limited number of choices for pitch and length of off-the-shelf synchronous belts, which translates into the need of fine-adjusting either the center distance or the law of motion. Differently from other approaches reported in the technical literature, the suggested method is based on the numerical solution of a set of functional equations. A numerical example shows application of the proposed method to a case study. Copyright © 2006 by ASME
Co-registrazione di immagini deformabile in radioterapia: metodi, assicurazione di qualità ed applicazioni cliniche
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