A Gammaherpesvirus Cooperates with Interferon-alpha/beta-Induced IRF2 to Halt Viral Replication, Control Reactivation, and Minimize Host Lethality

The gammaherpesviruses, including Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. The precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV, and type I (alpha/beta) interferons (IFNαβ) regulate MHV68 reactivation from both B cells and macrophages by unknown mechanisms. Here we demonstrate that IFNβ is highly upregulated during latent infection, in the absence of detectable MHV68 replication. We identify an interferon-stimulated response element (ISRE) in the MHV68 M2 gene promoter that is bound by the IFNαβ-induced transcriptional repressor IRF2 during latency in vivo. The M2 protein regulates B cell signaling to promote establishment of latency and reactivation. Virus lacking the M2 ISRE (ISREΔ) overexpresses M2 mRNA and displays uncontrolled acute replication in vivo, higher latent viral load, and aberrantly high reactivation from latency. These phenotypes of the ISREΔ mutant are B-cell-specific, require IRF2, and correlate with a significant increase in virulence in a model of acute viral pneumonia. We therefore identify a mechanism by which a gammaherpesvirus subverts host IFNαβ signaling in a surprisingly cooperative manner, to directly repress viral replication and reactivation and enforce latency, thereby minimizing acute host disease. Since we find ISREs 5′ to the major lymphocyte latency genes of multiple rodent, primate, and human gammaherpesviruses, we propose that cooperative subversion of IFNαβ-induced IRFs to promote latent infection is an ancient strategy that ensures a stable, minimally-pathogenic virus-host relationship

Signal transduction-related responses to phytohormones and environmental challenges in sugarcane

BACKGROUND: Sugarcane is an increasingly economically and environmentally important C4 grass, used for the production of sugar and bioethanol, a low-carbon emission fuel. Sugarcane originated from crosses of Saccharum species and is noted for its unique capacity to accumulate high amounts of sucrose in its stems. Environmental stresses limit enormously sugarcane productivity worldwide. To investigate transcriptome changes in response to environmental inputs that alter yield we used cDNA microarrays to profile expression of 1,545 genes in plants submitted to drought, phosphate starvation, herbivory and N(2)-fixing endophytic bacteria. We also investigated the response to phytohormones (abscisic acid and methyl jasmonate). The arrayed elements correspond mostly to genes involved in signal transduction, hormone biosynthesis, transcription factors, novel genes and genes corresponding to unknown proteins. RESULTS: Adopting an outliers searching method 179 genes with strikingly different expression levels were identified as differentially expressed in at least one of the treatments analysed. Self Organizing Maps were used to cluster the expression profiles of 695 genes that showed a highly correlated expression pattern among replicates. The expression data for 22 genes was evaluated for 36 experimental data points by quantitative RT-PCR indicating a validation rate of 80.5% using three biological experimental replicates. The SUCAST Database was created that provides public access to the data described in this work, linked to tissue expression profiling and the SUCAST gene category and sequence analysis. The SUCAST database also includes a categorization of the sugarcane kinome based on a phylogenetic grouping that included 182 undefined kinases. CONCLUSION: An extensive study on the sugarcane transcriptome was performed. Sugarcane genes responsive to phytohormones and to challenges sugarcane commonly deals with in the field were identified. Additionally, the protein kinases were annotated based on a phylogenetic approach. The experimental design and statistical analysis applied proved robust to unravel genes associated with a diverse array of conditions attributing novel functions to previously unknown or undefined genes. The data consolidated in the SUCAST database resource can guide further studies and be useful for the development of improved sugarcane varieties

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM

As necessidades comunicacionais das práticas educativas na prevenção da transmissão materno-fetal do HIV Communication needs of education practices in preventing maternal-fetal HIV transmission

OBJETIVOS: elucidar a fecundidade da prática educativa centrada na prevenção da transmissão materno-fetal da AIDS para promover a comunicação usuárias-serviços. MÉTODOS: Estudo exploratório, parte de uma pesquisa sobre atenção pré-natal, realizado em 19 centros de saúde, duas maternidades e seis unidades de saúde da família da Secretaria de Saúde da cidade do Recife, de maio a julho de 1998. O processo de trabalho foi observado, equipes técnicas entrevistadas e um questionário foi aplicado às 355 mulheres em atendimento; dessas, 81 foram submetidas à sondagem. RESULTADOS: nenhum serviço faz aconselhamento, mesmo quando informam sobre o teste anti-HIV (48,1%). O trabalho educativo está focalizado no fornecimento de informações durante a consulta, pois, as atividades coletivas, nas unidades que realizam-nas (48,1%), não ocorrem em todos os horários do pré-natal. A prática educativa baseada na racionalidade estratégica subestima a importância da aproximação às decisões valorativas das mulheres, das quais somente 11,1% utilizam camisinha de modo sistemático. CONCLUSÕES: a pequena oferta de atividades educativas no pré-natal e o "monólogo tecnocrático" que predomina nas relações entre usuárias e serviços de saúde têm repercussões negativas na vulnerabilidade da população feminina e de seus filhos.<br>OBJECTIVES: to determine the efficiency of educational methods in preventing maternal-fetal AIDS transmission through communication among users and health services providers. METHODS: exploratory study, part of the survey on pre-natal care, accomplished in 19 clinics, two maternity hospitals and six family health units performed by the Health Secretariat of the city of Recife, from May to July, 1998. Procedures were observed, technical teams were interviewed and questionnaires applied to 355 women being seen, of these, 81 participated of the survey. RESULTS: healthcare providers do not perform counseling, even when informing on HIV testing (48,1%). Education work is focused on furnishing information during consultation, for, collective activities in the units doing them (48,1%) do not occur in all of the pre-natal care schedules. Education based on strategic rationality underestimates the value of women's informed choice of which only 11,1% used condoms o a systematic way. CONCLUSIONS: insufficient education during pre-natal care and a "technocratic monologue" prevailing on the relationship between users and healthcare providers have a negative impact on the vulnerability of the female population and their children

https://doi.org/10.1016/j.quaint.2020.07.022

A correlation of stratigraphic subdivisions of the late Middle Pleistocene (MIS 12-6) in central Europe is extremely difficult, because of abundant hiatuses. Therefore, the site Rechitsa in western Belarus is extremely important for a regional stratigraphy, because of its well documented sediments of the Alexandrian Interglacial (Holsteinian; MIS 11) and a crucial palaeoclimate and palaeoenvironmental record of the Middle Pleistocene. The sequence starts with proglacial delta deposits formed at the termination of the Berezinian Glaciation (Elsterian; MIS 12), overlain by organic deposits of the Alexandrian Interglacial (Holsteinian; MIS 11) and the early glacial cooling of the Pripyatian Glaciation (Saalian). The hiatuses in MIS 10, 9 and 7 are interrupted by occasional occurrence of a periglacial lake, accompanied with open vegetation communities in MIS 8, characteristic by alternate temperate and cold episodes with significant climate-induced environmental transformations with extremely cold and dry conditions recorded by huge frost wedges with primary infilling. Extremely severe climatic conditions of MIS 6 favoured development of huge frost wedges with primary infilling, overlain by sediments of a periglacial lake. The Rechitsa section was overbuilt by glaciofluvial and aeolian deposits during the Pripyatian Glaciation (Saalian). The recorded huge hiatuses in MIS 10, 9 and 7 are common in central Europe represent presumably arid conditions and lack of deposition. The sedimentary sequence at the site Rechitsa is an important link of central and eastern European stratigraphic subdivisions of the Middle Pleistocene