Two-neutron transfer in 7 Be + 9 Be collisions

Elastic scattering and transfer cross sections for the 7 Be + 9 Be system have been measured at E lab = 23.1 MeV using the 7 Be radioactive secondary beam produced at Radioactive Ion Beams in Brazil facility at the University of São Paulo. The elastic scattering has been measured by detecting the 7 Be scattered at forward angles in the laboratory system. The transfer reaction 9 Be ( 7 Be , 9 Be ) 7 Be was identified by detecting the 9 Be scattered at the same laboratory angles. The elastic angular distribution has been analyzed by optical model calculations using a Woods-Saxon form factor whose parameters have been varied to best reproduce the experimental data at forward angles. Coupled reaction channels calculations (CRC) have been performed to describe the transfer, considering the coupling to the transfer channel and including contributions to the ground state and to the first excited state of 7 Be ( 1 / 2 − ; 429 keV ) in the final state. The spectroscopic amplitudes used in the CRC calculation have been derived from shell-model calculations. Similar CRC calculations were applied to existing 9 Be ( p , t ) 7 Be data to check the consistency of our results results for the ( 7 Be , 9 Be ) transfer reaction.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) de Brasil, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) de Brasil y Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) de Brasil. 2013/22100-7 y 2016/21434-

Immunophenotyping of peripheral blood, lymph node, and bone marrow T lymphocytes during canine leishmaniosis and the impact of antileishmanial chemotherapy

Dogs are a major reservoir of Leishmania infantum, etiological agent of canine leishmaniosis (CanL) a zoonotic visceral disease of worldwide concern. Therapeutic protocols based on antileishmanial drugs are commonly used to treat sick dogs and improve their clinical condition. To better understand the impact of Leishmania infection and antileishmanial drugs on the dog's immune response, this study investigates the profile of CD4+ and CD8+ T cell subsets in peripheral blood, lymph node, and bone marrow of sick dogs and after two different CanL treatments. Two CanL groups of six dogs each were treated with either miltefosine or meglumine antimoniate combined with allopurinol. Another group of 10 clinically healthy dogs was used as control. Upon diagnosis and during the following 3 months of treatment, peripheral blood, popliteal lymph node, and bone marrow mononuclear cells were collected, labeled for surface markers CD45, CD3, CD4, CD8, CD25, and intracellular nuclear factor FoxP3, and T lymphocyte subpopulations were immunophenotyped by flow cytometry. CanL dogs presented an overall increased frequency of CD8+ and CD4+CD8+ double-positive T cells in all tissues and a decreased frequency of CD4+ T cells in the blood. Furthermore, there was a higher frequency of CD8+ T cells expressing CD25+FoxP3+ in the blood and bone marrow. During treatment, these subsets recovered to levels similar to those of healthy dogs. Nevertheless, antileishmanial therapy caused an increase of CD4+CD25+FoxP3+ T cells in all tissues, associated with the decrease of CD8+CD25−FoxP3− T cell percentages. These findings may support previous studies that indicate that L. infantum manipulates the dog's immune system to avoid the development of a protective response, ensuring the parasite's survival and the conditions that allow the completion of Leishmania life cycle. Both treatments used appear to have an effect on the dog's immune response, proving to be effective in promoting the normalization of T cell subsets.publishersversionpublishe

immune activation of canine hepatic spheroids exposed to leishmania infantum

The application of innovative three-dimensional (3D) spheroids cell culture strategy to Parasitology offers the opportunity to closely explore host–parasite interactions. Here we present a first report on the application of 3D hepatic spheroids to unravel the immune response of canine hepatocytes exposed to Leishmania infantum. The liver, usually considered a major metabolic organ, also performs several important immunological functions and constitutes a target organ for L. infantum infection, the etiological agent of canine leishmaniasis (CanL), and a parasitic disease of major veterinary and public health concern. 3D hepatic spheroids were able to sense and immunologically react to L. infantum parasites, generating an innate immune response by increasing nitric oxide (NO) production and enhancing toll-like receptor (TLR) 2 and interleukin-10 gene expression. The immune response orchestrated by canine hepatocytes also lead to the impairment of several cytochrome P450 (CYP450) with possible implications for liver natural xenobiotic metabolization capacity. The application of meglumine antimoniate (MgA) increased the inflammatory response of 3D hepatic spheroids by inducing the expression of Nucleotide oligomerization domain (NOD)-like receptors 1 and NOD2 and TLR2, TLR4, and TLR9 and enhancing gene expression of tumour necrosis factor α. It is therefore suggested that hepatocytes are key effector cells and can activate and orchestrate the immune response to L. infantum parasites.publishersversionpublishe

Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.publishersversionpublishe

A genome survey of Moniliophthora perniciosa gives new insights into Witches' Broom Disease of cacao

<p>Abstract</p> <p>Background</p> <p>The basidiomycete fungus <it>Moniliophthora perniciosa </it>is the causal agent of Witches' Broom Disease (WBD) in cacao (<it>Theobroma cacao</it>). It is a hemibiotrophic pathogen that colonizes the apoplast of cacao's meristematic tissues as a biotrophic pathogen, switching to a saprotrophic lifestyle during later stages of infection. <it>M. perniciosa</it>, together with the related species <it>M. roreri</it>, are pathogens of aerial parts of the plant, an uncommon characteristic in the order Agaricales. A genome survey (1.9× coverage) of <it>M. perniciosa </it>was analyzed to evaluate the overall gene content of this phytopathogen.</p> <p>Results</p> <p>Genes encoding proteins involved in retrotransposition, reactive oxygen species (ROS) resistance, drug efflux transport and cell wall degradation were identified. The great number of genes encoding cytochrome P450 monooxygenases (1.15% of gene models) indicates that <it>M. perniciosa </it>has a great potential for detoxification, production of toxins and hormones; which may confer a high adaptive ability to the fungus. We have also discovered new genes encoding putative secreted polypeptides rich in cysteine, as well as genes related to methylotrophy and plant hormone biosynthesis (gibberellin and auxin). Analysis of gene families indicated that <it>M. perniciosa </it>have similar amounts of carboxylesterases and repertoires of plant cell wall degrading enzymes as other hemibiotrophic fungi. In addition, an approach for normalization of gene family data using incomplete genome data was developed and applied in <it>M. perniciosa </it>genome survey.</p> <p>Conclusion</p> <p>This genome survey gives an overview of the <it>M. perniciosa </it>genome, and reveals that a significant portion is involved in stress adaptation and plant necrosis, two necessary characteristics for a hemibiotrophic fungus to fulfill its infection cycle. Our analysis provides new evidence revealing potential adaptive traits that may play major roles in the mechanisms of pathogenicity in the <it>M. perniciosa</it>/cacao pathosystem.</p

Cutoff Scanning Matrix (CSM): structural classification and function prediction by protein inter-residue distance patterns

BACKGROUND: The unforgiving pace of growth of available biological data has increased the demand for efficient and scalable paradigms, models and methodologies for automatic annotation. In this paper, we present a novel structure-based protein function prediction and structural classification method: Cutoff Scanning Matrix (CSM). CSM generates feature vectors that represent distance patterns between protein residues. These feature vectors are then used as evidence for classification. Singular value decomposition is used as a preprocessing step to reduce dimensionality and noise. The aspect of protein function considered in the present work is enzyme activity. A series of experiments was performed on datasets based on Enzyme Commission (EC) numbers and mechanistically different enzyme superfamilies as well as other datasets derived from SCOP release 1.75. RESULTS: CSM was able to achieve a precision of up to 99% after SVD preprocessing for a database derived from manually curated protein superfamilies and up to 95% for a dataset of the 950 most-populated EC numbers. Moreover, we conducted experiments to verify our ability to assign SCOP class, superfamily, family and fold to protein domains. An experiment using the whole set of domains found in last SCOP version yielded high levels of precision and recall (up to 95%). Finally, we compared our structural classification results with those in the literature to place this work into context. Our method was capable of significantly improving the recall of a previous study while preserving a compatible precision level. CONCLUSIONS: We showed that the patterns derived from CSMs could effectively be used to predict protein function and thus help with automatic function annotation. We also demonstrated that our method is effective in structural classification tasks. These facts reinforce the idea that the pattern of inter-residue distances is an important component of family structural signatures. Furthermore, singular value decomposition provided a consistent increase in precision and recall, which makes it an important preprocessing step when dealing with noisy data