Substituent effects on the nitrogen-15 and carbon-13 shieldings of some N-arylguanidinium chlorides

The 13C and 15N chemical shifts of five N-arylguanidinium chlorides carrying polar substituents, ranging in character from 4-methoxy to 4-nitro groups, have been determined by NMR spectroscopy at the natural-abundance level of 13C and 15N in dimethyl sulfoxide solution. Comparison of the 13C shifts of these salts with those of monosubstituted benzenes shows that the guanidinium group induces an average downfield shift of -5.8 ppm of the resonance of the aryl carbon to which it is attached (C1), an average upfield shift of +4.2 ppm for C2 and C6, and a small upfield shift of +1.9 ppm for C4. The shifts of C3 and C5 are small and erratic relative to the corresponding carbons in monosubstituted benzenes. The 15N resonances of the guanidinium nitrogens are quite sensitive to electric effects resulting from substitution of polar groups at C4. The 15N shift of the ==NAr nitrogen relative to that of the salts suggests that the predominant tautomer for N-arylguanidines is (H2N)2C==NAr. The 15N shifts of the (NH2) 2 nitrogens correlate rather well with σp- parameters, whereas the shifts of the -NHAr nitrogens seem to correlate only with R values derived from the σp- substituent constants

Pyroclasts of the first phases of the explosive-effusive PCCVC volcanic eruption: physicochemical analysis

The morphology, texture, grain size and other physicochemical characteristics of pyroclastic material from the first phases of the Puyehue-Cordon Caulle volcanic complex (PCCVC) eruption, (Southern Andes, Chile), can be associated to the model recently reported for the magma storage and its ascent conditions. The eruption started June 4th 2011, and the studied volcanic material corresponds to that collected in Argentine territory at different distances from the source, between 4 and 12 June 2011. The explosive-effusive volcanic process of the first days occurred with the simultaneous emplacement of lava flows and the venting of pyroclastic material, ejecting two well differentiated types of particles. The more abundant was constituted by rhyolitic and light color pumice fragments, characterized by a typical vesicular texture, easy fragmentation and absence of occluded crystalline phases. Particles found in minor proportion were dark color, different in shape and texture and rich in Fe and Ti. They seemed to be more effective for the interaction with emitted gases in the upper part of the column, for this reason, they appeared partially covered by condensation products. The ascent conditions of the magma affected its rheological behavior through variations in the degassing, viscosity and fragmentation. On the other hand, distance to the source, depositional time, volcanic evolution and environmental conditions are factors that affect the chemical composition of collected ash. So, the SiO2/FeO ratio not only increases with the distance but also with the deposition time and volcanic activity. The work was done with the aid of several techniques such as a laser-sediment analyzer, X-ray diffraction (XRD), chemical analysis (bulk and surface), SEM microscopy and Raman “microprobe” spectroscopy. On the other hand, the physicochemical behavior of the pyroclastic material allows us to suggest eventual applications

Towards biological control strategies for the bronze bug, Thaumastocoris peregrinus, on eucalyptus plantations in South America.

Edição dos abstracts do 24º IUFRO World Congress, 2014, Salt Lake City. Sustaining forests, sustaining people: the role of research

Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance

Complement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa(−/−)) or C3 (C3(−/−)) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa(−/−) or C3(−/−) mice. The rejection of the male grafts correlated with the presence of HY D(b)Uty-specific CD8(+) T cells. Consistent with this, peptide-treated C1qa(−/−) and C3(−/−) female mice rejecting male grafts exhibited more antigen-specific CD8(+)IFN-γ(+) and CD8(+)IL-10(+) cells compared with WT females. This suggests that accumulation of IFN-γ- and IL-10-producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide-treated WT mice, IFN-γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance

Serum Amyloid P Aids Complement-Mediated Immunity to Streptococcus pneumoniae

The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been reported. We have investigated the role of SAP for innate immunity to the important human pathogen Streptococcus pneumoniae. Using flow cytometry assays, we show that SAP binds to S. pneumoniae, increases classical pathway–dependent deposition of complement on the bacteria, and improves the efficiency of phagocytosis. As a consequence, in mouse models of infection, mice genetically engineered to be SAP-deficient had an impaired early inflammatory response to S. pneumoniae pneumonia and were unable to control bacterial replication, leading to the rapid development of fatal infection. Complement deposition, phagocytosis, and control of S. pneumoniae pneumonia were all improved by complementation with human SAP. These results demonstrate a novel and physiologically significant role for SAP for complement-mediated immunity against an important bacterial pathogen, and provide further evidence for the importance of the classical complement pathway for innate immunity

A Neutral and Stable Macrocyclic Mn(II) Complex for MRI Tumor Visualization

A stable and inert amphiphilic Mn(II) complex based on a bisamide derivative of 1,4-DO2A (DO2A=tetraazacyclododecane-1,4-diacetic acid) was synthesized and its H-1 NMR relaxometric behavior was investigated as a function of the magnetic field strength, pH and temperature. The interaction with human serum albumin (HSA) was also studied via relaxometry showing a good relaxivity enhancement at low field (at 1T and 298 K the relaxivity increases from 4.5 mM(-1) s(-1) of the Mn(II)-complex to 14.0 mM(-1) s(-1) of the complex-HSA supramolecular adduct). In vivo biodistribution and MRI studies highlighted a rapid and mixed renal/liver elimination without spleen accumulation from healthy mice and good contrast enhancing properties in a breast tumor murine model. A comparison with a clinically approved Gd(III) agent (GdBOPTA, Multihance (R)) underlined that the proposed Mn(II) contrast agent gave comparable tumor contrast enhancement up to 3 hours post-injection

Quantitative MRI Measurement of Binder Distributions in Green-State Ceramics

Development of reliable and improved structural ceramics for advanced heat engines and other applications requires process diagnostics and materials evaluation from powder preparation to green-body forming to final sintering. Injection molding is a promising processing method being developed for mass production of complex-shaped heat engine components such as turbochargers (rotors and stator vanes) and engine valves. Major processing steps in injection-molded ceramic manufacturing include preparation of ceramic powders and organic binders, mixing, molding, binder removal, sintering, and finishing [1]. While materials evaluation and diagnostics are needed throughout the process, it is particularly important to evaluate the distributions of binders/plasticizers in as-molded green bodies [2]. Poor distribution of these organics in a green body can lead to a final part that is defective or that has poor mechanical properties after it is sintered

Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo

Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa−/−). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo

International Undiagnosed Diseases Programs (UDPs): components and outcomes

Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature. This exploration allowed for an assessment of the strengths and limitations of each of the six common steps, namely enrollment, comprehensive clinical phenotyping, research diagnostics, data sharing and matchmaking, results, and follow-up. Current literature highlights the potential utility of Undiagnosed Diseases Programs in research diagnostics. Since participants have often had extensive previous genetic studies, research pipelines allow for diagnostic approaches beyond exome or whole genome sequencing, through reanalysis using research-grade bioinformatics tools and multi-omics technologies. The overall diagnostic yield is presented by study, since different selection criteria at enrollment and reporting processes make comparisons challenging and not particularly informative. Nonetheless, diagnostic yield in an undiagnosed cohort reflects the potential of an Undiagnosed Diseases Program. Further comparisons and exploration of the outcomes of Undiagnosed Diseases Programs worldwide will allow for the development and improvement of the diagnostic and research process and in turn improve the value and utility of an Undiagnosed Diseases Program

Trypanosomatid infections among vertebrates of Chile: a systematic review

We present a review on the natural infection by trypanosomatids of nonhuman vertebrates in Chile, aiming to synthesize and update the knowledge on the diversity of trypanosomatids infecting native and alien vertebrate species. To this end, we conducted a systematic review of literature records published from 1900 to April 2020 on four databases, focusing on the 21 genera of trypanosomatids and Chile. The methods and findings of our review have been based on the preferred reporting items for systematic reviews and meta-analysis (prisma) checklist. We found 29,756 records but only 71 presented relevant information for this review. Overall, there are only two reported trypanosomatid genera infecting vertebrate species in Chile, the genera Trypanosoma and Leishmania. The former is mostly represented by Trypanosoma cruzi (90% of the total records) and to a much lesser extent by Trypanosoma avium, Trypanosoma humboldti, Trypanosoma lewisi, and a couple of unidentified trypanosomatids. A total of 25 mammals have been reported as being infected by T. cruzi, including 14 native and 11 alien species from Orders Artiodactyla, Carnivora, Chiroptera, Didelphimorphia, Lagomorpha, Perissodactyla, and Rodentia. Extensive screening studies using new analytical tools are necessary to grasp the whole potential diversity of trypanosomatid species infecting vertebrates in Chile