Recomendações de inseticidas para utilização no programa de manejo de pragas da soja, safra 1983/84, nos Estados de Mato Grosso do Sul, Paraná e São Paulo.

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Recomendações de inseticidas para utilização no programa de manejo de pragas da soja - safra 1981/82 - nos Estados do Paraná, São Paulo e Mato Grosso do Sul.

bitstream/item/53974/1/11.pd

Recomendacoes de inseticidas para utilizacao no Programa de Manejo de Pragas da Soja safra 1982/83 nos Estados de Mato Grosso do Sul, Parana e Sao Paulo.

bitstream/item/53973/1/17.pd

Workforce requirements in rheumatology: a systematic literature review informing the development of a workforce prediction risk of bias tool and the EULAR points to consider

Objective: To summarise the available information on physician workforce modelling, to develop a rheumatology workforce prediction risk of bias tool and to apply it to existing studies in rheumatology. Methods: A systematic literature review (SLR) was performed in key electronic databases (1946–2017) comprising an update of an SLR in rheumatology and a hierarchical SLR in other medical fields. Data on the type of workforce prediction models and the factors considered in the models were extracted. Key general as well as specific need/demand and supply factors for workforce calculation in rheumatology were identified. The workforce prediction risk of bias tool was developed and applied to existing workforce studies in rheumatology. Results: In total, 14 studies in rheumatology and 10 studies in other medical fields were included. Studies used a variety of prediction models based on a heterogeneous set of need/demand and/or supply factors. Only two studies attempted empirical validation of the prediction quality of the model. Based on evidence and consensus, the newly developed risk of bias tool includes 21 factors (general, need/demand and supply). The majority of studies revealed high or moderate risk of bias for most of the factors. Conclusions: The existing evidence on workforce prediction in rheumatology is scarce, heterogeneous and at moderate or high risk of bias. The new risk of bias tool should enable future evaluation of workforce prediction studies. This review informs the European League Against Rheumatism points to consider for the conduction of workforce requirement studies in rheumatology

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity

Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2

Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK). The specific structural differences in VRK catalytic sites make them suitable candidates for development of specific inhibitors. In this work we have determined the sensitivity of VRK1 and VRK2 to kinase inhibitors, currently used in biological assays or in preclinical studies, in order to discriminate between the two proteins as well as with respect to the vaccinia virus B1R kinase. Both VRK proteins and vaccinia B1R are poorly inhibited by inhibitors of different types targeting Src, MEK1, B-Raf, JNK, p38, CK1, ATM, CHK1/2 and DNA-PK, and most of them have no effect even at 100 µM. Despite their low sensitivity, some of these inhibitors in the low micromolar range are able to discriminate between VRK1, VRK2 and B1R. VRK1 is more sensitive to staurosporine, RO-31-8220 and TDZD8. VRK2 is more sensitive to roscovitine, RO 31–8220, Cdk1 inhibitor, AZD7762, and IC261. Vaccinia virus B1R is more sensitive to staurosporine, KU55933, and RO 31–8220, but not to IC261. Thus, the three kinases present a different pattern of sensitivity to kinase inhibitors. This differential response to known inhibitors can provide a structural framework for VRK1 or VRK2 specific inhibitors with low or no cross-inhibition. The development of highly specific VRK1 inhibitors might be of potential clinical use in those cancers where these kinases identify a clinical subtype with a poorer prognosis, as is the case of VRK1 in breast cancer